Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study.

BACKGROUND AND AIMS: In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm-control therapy. Predictors of attaining sinus rhythm at follow-up are not well known. METHODS: To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 46% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets. RESULTS: Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR] 0.76 [95% confidence interval 0.65-0.89], p=0.001), bone morphogenetic protein 10 (BMP10) (OR 0.83 [0.71-0.97], p=0.017) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR 0.73 [0.60-0.88], p=0.001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (pinteraction=0.033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR 0.64 [0.51-0.80], p<0.001; early rhythm control: OR 0.90 [0.69-1.18], p=0.453). External validation confirmed that low concentrations of ANGPT2, BMP10 and NT-proBNP predict sinus rhythm during follow-up. CONCLUSIONS: Low concentrations of ANGPT2, BMP10 and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.

Subclinical Atrial Fibrillation: A Silent Threat with Uncertain Implications.

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Implantable and wearable cardiac devices have enabled the detection of asymptomatic AF episodes-termed subclinical AF (SCAF). SCAF, the prevalence of which is likely significantly underestimated, is associated with increased cardiovascular and all-cause mortality and a significant stroke risk. Recent advances in machine learning, namely artificial intelligence-enabled ECG (AI-ECG), have enabled identification of patients at higher likelihood of SCAF. Leveraging the capabilities of AI-ECG algorithms to drive screening protocols could eventually allow for earlier detection and treatment and help reduce the burden associated with AF.

High Risk of Stroke in Patients With Worsening Heart Failure, Reduced Ejection Fraction, Coronary Heart Disease and Sinus Rhythm: Risk Prediction Score Analysis From the COMMANDER-HF Trial.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban. METHODS AND RESULTS: Stroke risk and treatment effect were computed across risk score and plasma d-dimer tertiles. Risk score was available in 58% of the COMMANDER-HF population (n = 2928). Over a median follow-up of 512 days (range 342-747 days), 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index = 0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P-interaction = .67). Among patients in whom the risk score was estimated, d-dimer was available in 2343 (80%). d-dimer had an acceptable discrimination performance for stroke prediction (C-index = 0.66) and higher plasma d-dimer concentrations were associated with higher rates of stroke (ie, tertile 3 vs tertile 1, hazard ratio 3.65, 95% confidence interval 1.59-8.39, P = .002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by d-dimer levels (ie, >515 ng/mL, hazard ratio 0.42, 95% confidence interval 0.18-0.95, P-interaction = .074), without any safety concerns. CONCLUSIONS: In our analysis, plasma d-dimer concentrations performed better than a previously described 3-variable risk score for stroke prediction in patients with heart failure with reduced ejection fraction, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma d-dimer concentration identified patients who might benefit most from rivaroxaban.

Single-lead electrocardiogram Artificial Intelligence model with risk factors detects atrial fibrillation during sinus rhythm.

AIMS: Guidelines recommend opportunistic screening for atrial fibrillation (AF), using a 30 s single-lead electrocardiogram (ECG) recorded by a wearable device. Since many patients have paroxysmal AF, identification of patients at high risk presenting with sinus rhythm (SR) may increase the yield of subsequent long-term cardiac monitoring. The aim is to evaluate an AI-algorithm trained on 10 s single-lead ECG with or without risk factors to predict AF. METHODS AND RESULTS: This retrospective study used 13 479 ECGs from AF patients in SR around the time of diagnosis and 53 916 age- and sex-matched control ECGs, augmented with 17 risk factors extracted from electronic health records. AI models were trained and compared using 1- or 12-lead ECGs, with or without risk factors. Model bias was evaluated by age- and sex-stratification of results. Random forest models identified the most relevant risk factors. The single-lead model achieved an area under the curve of 0.74, which increased to 0.76 by adding six risk factors (95% confidence interval: 0.74-0.79). This model matched the performance of a 12-lead model. Results are stable for both sexes, over ages ranging from 40 to 90 years. Out of 17 clinical variables, 6 were sufficient for optimal accuracy of the model: hypertension, heart failure, valvular disease, history of myocardial infarction, age, and sex. CONCLUSION: An AI model using a single-lead SR ECG and six risk factors can identify patients with concurrent AF with similar accuracy as a 12-lead ECG-AI model. An age- and sex-matched data set leads to an unbiased model with consistent predictions across age groups.

Human induced pluripotent stem cell-derived atrial cardiomyocytes recapitulate contribution of the slowly activating delayed rectifier currents IKs to repolarization in the human atrium.

AIMS: Human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCM) could be a helpful tool to study the physiology and diseases of the human atrium. To fulfil this expectation, the electrophysiology of hiPSC-aCM should closely resemble the situation in the human atrium. Data on the contribution of the slowly activating delayed rectifier currents (IKs) to repolarization are lacking for both human atrium and hiPSC-aCM. METHODS AND RESULTS: Human atrial tissues were obtained from patients with sinus rhythm (SR) or atrial fibrillation (AF). Currents were measured in human atrial cardiomyocytes (aCM) and compared with hiPSC-aCM and used to model IKs contribution to action potential (AP) shape. Action potential was recorded by sharp microelectrodes. HMR-1556 (1 µM) was used to identify IKs and to estimate IKs contribution to repolarization. Less than 50% of hiPSC-aCM and aCM possessed IKs. Frequency of occurrence, current densities, activation/deactivation kinetics, and voltage dependency of IKs did not differ significantly between hiPSC-aCM and aCM, neither in SR nor AF. ß-Adrenoceptor stimulation with isoprenaline did not increase IKs neither in aCM nor in hiPSC-aCM. In tissue from SR, block of IKs with HMR-1556 did not lengthen the action potential duration, even when repolarization reserve was reduced by block of the ultra-rapid repolarizing current with 4-aminopyridine or the rapidly activating delayed rectifier potassium outward current with E-4031. CONCLUSION: I Ks exists in hiPSC-aCM with biophysics not different from aCM. As in adult human atrium (SR and AF), IKs does not appear to relevantly contribute to repolarization in hiPSC-aCM.

Initial Holter Electrocardiogram Index to Predict the Burden of Subsequent Persistent Premature Ventricular Complex in Childhood.

BACKGROUND: Asymptomatic premature ventricular complex (PVC) in childhood often disappears over time. However, predictive factors for persistent PVC are unknown. We examined predictive factors for persistent PVCs on initial Holter electrocardiogram (ECG) in pediatric patients with asymptomatic PVC.Methods and Results: The initial Holter ECG findings of untreated PVC patients (n=216) between 2010 and 2021 were examined. Multivariable analysis was performed to clarify predictive factors for subsequent persistent PVC burden for each index (age, sex, PVC burden, PVC origin, minimum and maximum mean RR intervals [RRmin and RRmax, respectively]) of the 3 heartbeats of baseline sinus rhythm immediately before the PVC. The median age at initial Holter ECG was 11.6 years (range 5.8-18.8 years), the PVC burden was 5.22% (range 0.01-44.21%), RRmin was 660 ms, RRmax was 936 ms, RRrange (=RRmax-RRmin) was 273 ms, and 15 (7%) PVC runs were identified. The median follow-up period was 5.1 years (range 0.8-9.4 years), and the final Holter PVC burden was 3.99% (range 0-36.38%). In multivariate analysis, RRrange was the only independent risk factor for predicting a final Holter PVC burden >10%, with an area under the curve of 0.920 using an RRrange of 600 ms as the cut-off value. CONCLUSIONS: A wide RRrange at the initial Holter ECG may be a predictive indicator for persistent PVC in childhood.

Isolated non-immune-mediated second-degree atrioventricular block in the fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To determine the clinical course of fetal isolated non-immune-mediated second-degree atrioventricular block (AVB) and the factors associated with spontaneous recovery in these cases. METHODS: Fetuses with isolated non-immune-mediated second-degree AVB were recruited prospectively between 2014 and 2022. These fetuses were divided into two groups: those which recovered spontaneously and those which did not. Maternal and fetal characteristics and intrauterine and postnatal outcomes were compared between the two groups. RESULTS: The study cohort included 20 fetuses with isolated non-immune-mediated second-degree AVB, diagnosed at a median gestational age of 22.0 (range, 17.0-35.0) weeks. In 12 fetuses, 1:1 atrioventricular conduction was restored spontaneously in utero and there was no recurrence during the postnatal follow-up period. In the remaining eight fetuses, second-degree AVB was maintained and, in six of these, the pregnancy was terminated on parental request. Of the two liveborn children who had persistent second-degree AVB prenatally, one had progressed to complete AVB at the latest follow-up, at the age of 34 months, but was asymptomatic, without heart enlargement or dysfunction. The other child progressed to complete AVB after delivery and was diagnosed with type-2 long QT syndrome. This infant died aged 2 months. Fetuses in the group that recovered spontaneously had earlier gestational age at diagnosis (median, 20.0 (range, 17.0-26.0) vs 24.5 (range, 18.0-35.0) weeks; P = 0.004) and higher atrial rate at diagnosis (median, 147 (range, 130-160) vs 138 (range, 125-149) bpm; P = 0.006) in comparison with the group that did not recover spontaneously. The best cut-off values for prediction of failure to recover spontaneously were 22.5 weeks' gestational age at diagnosis and 144 bpm atrial rate at diagnosis, with sensitivities of 87.5% and 75.0%, respectively, and specificities of 92.0% and 87.5%, respectively. CONCLUSIONS: The outcome of 60% of fetuses with isolated non-immune-mediated second-degree AVB was favorable. Earlier gestational age and higher atrial rate at diagnosis were associated with spontaneous reversion to normal sinus rhythm. Prenatal genetic testing should be performed in cases with persistent AVB, to exclude heritable disorders including long QT syndrome. These findings provide important information for clinical management and prenatal counseling in these cases. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Effectiveness of a Triple Antiarrhythmic Drug Strategy for Arrhythmia Recurrence after Persistent Atrial Fibrillation Ablation.

BACKGROUND AND OBJECTIVE: Treating recurrent atrial arrhythmias after persistent atrial fibrillation (PeAF) ablation is often challenging. This single-center, prospective study aimed to observe the effectiveness of different combinations of oral antiarrhythmic drugs (AADs) in reverting to sinus rhythm (SR) in patients with recurrent atrial arrhythmias after PeAF ablation. METHODS: Forty-five patients who experienced recurrent atrial arrhythmias after PeAF ablation were included. Based on their medication regimens, patients were divided into two groups, with the study group being a triple-drug group (digoxin combined with amiodarone/ propafenone and ß-blocker), and the control group being a non-triple-drug group. RESULTS: The rate of reversion to SR was significantly higher in the study group (n = 29) than in the control group (n = 16) at 3 weeks (34.48% vs. 0%, p < 0.01) and 1 month (44.84% vs. 6.25%, p = 0.02) after initiating AADs. No patients with asymptomatic bradycardia were observed in either group. CONCLUSIONS: For patients with recurrent atrial arrhythmias after PeAF ablation, a regimen of low-dose digoxin combined with amiodarone/propafenone and ß-blocker may effectively improve short-term reversion rates.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

Comparison of initial adenosine dose conversion rate for supraventricular tachycardia in the emergency department.

OBJECTIVE: To evaluate the rate of supraventricular tachycardia (SVT) termination between 6 mg and 12 mg initial adenosine doses. METHODS: This multi-center, retrospective cohort study evaluated patients presenting to the emergency department (ED) from January 1, 2020 to June 30, 2022 in SVT and received adenosine. The primary objective of the study is to compare the rate of SVT termination between adenosine 6 mg and 12 mg as documented on a formal electrocardiogram. Secondary endpoints include termination of SVT with subsequent adenosine dose, time to ED disposition, adverse effects, and subgroup analyses of patients with a body mass index greater than or equal to 40 kg/m2 and a history of SVT. RESULTS: Of 213 patients included, a 6 mg initial adenosine dose was administered to 117 patients (54.9 %) and a 12 mg initial adenosine dose was administered to 96 patients (45.1 %). SVT termination following the initial dose of 6 mg or 12 mg was 56.4 % and 79.1 %, respectively (p < 0.001). Among the 46 patients who failed to terminate SVT with an initial 6 mg dose, 33 converted to sinus rhythm with a subsequent adenosine dose in comparison to 1 of the 7 patients receiving an initial dose of 12 mg (71.7 % vs 14.3 %, p = 0.007). Median time to ED disposition, either inpatient admission or discharge, was 209 and 161 min, respectively (p = 0.104). There was no statistical difference in either subgroup analyses. CONCLUSION: A higher rate of SVT termination was observed with an initial adenosine dose of 12 mg in the ED in comparison to the guideline recommended dose of 6 mg. There were no significant differences in adverse effects observed.

Outcomes of Concomitant Maze Procedure in Tricuspid Repair for Severe Tricuspid Regurgitation.

BACKGROUND: We aimed to analyze the impact of concomitant Maze procedure on the clinical and rhythm outcomes, and echocardiographic parameters in tricuspid repair for patients with severe tricuspid regurgitation (TR) and persistent atrial fibrillation (AF). METHODS: Patients who had severe TR and persistent AF and underwent tricuspid valve (TV) repair were included in the study. Both primary TR and secondary TR were included in the current study. The study population was stratified according to Maze procedure. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE) at 15 years post-surgery. Propensity-score matching analyses was performed to adjust baseline differences. RESULTS: Three hundred seventy-one patients who underwent tricuspid repair for severe TR and persistent AF from 1994 to 2021 were included, and 198 patients (53.4%) underwent concomitant Maze procedure. The maze group showed 10-year sinus rhythm (SR) restoration rate of 55%. In the matched cohort, the maze group showed a lower cumulative incidence of cardiac death (4.6% vs. 14.4%, P = 0.131), readmission for heart failure (8.1% vs. 22.2%, P = 0.073), and MACCE (21.1% vs. 42.1%, P = 0.029) at 15 years compared to the non-maze group. Left atrial (LA) diameter significantly decreased in the maze group at 5 years (53.3 vs. 59.6 mm, P < 0.001) after surgery compared to preoperative level, and there was a significant difference in the change of LA diameter over time between the two groups (P = 0.013). CONCLUSION: The Maze procedure during TV repair in patients with severe TR and persistent AF showed acceptable SR rates and lower MACCE rates compared to those without the procedure, while also promoting LA reverse remodeling.

Exosomal miRNA Changes Associated with Restoration to Sinus Rhythm in Atrial Fibrillation Patients.

We aimed to identify serum exosomal microRNAs (miRNAs) associated with the transition from atrial fibrillation (AF) to sinus rhythm (SR) and investigate their potential as biomarkers for the early recurrence of AF within three months post-treatment. We collected blood samples from eight AF patients at Chang Gung Memorial Hospital in Taiwan both immediately before and within 14 days following rhythm control treatment. Exosomes were isolated from these samples, and small RNA sequencing was performed. Using DESeq2 analysis, we identified nine miRNAs (16-2-3p, 22-3p, 23a-3p, 23b-3p, 125a-5p, 328-3p, 423-5p, 504-5p, and 582-3p) associated with restoration to SR. Further analysis using the DIABLO model revealed a correlation between the decreased expression of miR-125a-5p and miR-328-3p and the early recurrence of AF. Furthermore, early recurrence is associated with a longer duration of AF, presumably indicating a more extensive state of underlying cardiac remodeling. In addition, the reads were mapped to mRNA sequences, leading to the identification of 14 mRNAs (AC005041.1, ARHGEF12, AMT, ANO8, BCL11A, DIO3OS, EIF4ENIF1, G2E3-AS1, HERC3, LARS, NT5E, PITX1, SLC16A12, and ZBTB21) associated with restoration to SR. Monitoring these serum exosomal miRNA and mRNA expression patterns may be beneficial for optimizing treatment outcomes in AF patients.

Noninvasive ECG imaging of the intrinsic atrial pacemaker and atrial activation in surgically repaired or palliated congenital heart disease.

INTRODUCTION: Sinus node location, function, and atrial activation are often abnormal in patients with congenital heart disease (CHD), due to anatomical, surgical, and acquired factors. We aimed to perform noninvasive electrocardiographic imaging (ECGI) of the intrinsic atrial pacemaker and atrial activation in patients with surgically repaired or palliated CHD, compared with control patients with structurally normal hearts. METHODS AND RESULTS: Atrial ECGI was performed in eight CHD patients with prespecified diagnoses (Fontan circulation, dextro transposition of the great arteries post Mustard/Senning, tetralogy of Fallot), and three controls. Activation and propagation maps were constructed in presenting rhythm. Wavefront propagation was analyzed to identify (1) intrinsic atrial pacemaker breakout site, (2) morphological right atrial (RA) activation pattern, (3) morphological left atrial (LA) breakout sites (i.e., interatrial connections), (4) LA activation pattern, and (5) putative lines of block. Physiologically appropriate atrial activation and propagation maps were able to be constructed. In the majority of patients, atrial breakouts were in keeping with the sinus node, observed in a crescent-shaped distribution from the anterior superior vena cava to the posterior RA. Ectopic atrial pacemaker sites were demonstrated in the atriopulmonary (AP) Fontan patient (very diffuse posterolateral RA) and Mustard patient (very posterior RA competing with a low RA focus). RA propagation was laminar in controls, but suggested either a line of block or conduction slowing consistent with an atriotomy scar in the tetralogy of Fallot (TOF) patients. Putative lines of block were more complex and RA propagation more abnormal in the atrial switch and AP Fontan patients, compared with the TOF patients. RA activation in the extracardiac Fontan patients was relatively laminar. Earliest LA breakout was most commonly observed in the region of Bachmann's Bundle in both controls and CHD patients, except for posterior LA breakouts in two patients. LA activation was typically more homogeneous than RA activation in CHD patients. CONCLUSION: ECGI can be utilized to create a noninvasive mapping model of atrial activation in postsurgical CHD, demonstrating atrial pacemaker location, putative lines of block and interatrial connections. Once validated invasively, this may have clinical implications in predicting risk of sinus node dysfunction and atrial arrhythmias, or in guiding catheter ablation.

Guiding ablation strategies for ventricular tachycardia in patients with structural heart disease by analyzing links and conversion patterns of traceable abnormal late potential zone.

BACKGROUND: Substrate-based ablation can treat uninducible or hemodynamically instability scar-related ventricular tachycardia (VT). However, whether a correlation exists between the critical VT isthmus and late activation zone (LAZ) during sinus rhythm (SR) is unknown. OBJECTIVE: To demonstrate the structural and functional properties of abnormal substrates and analyze the link between the VT circuit and abnormal activity during SR. METHODS: Thirty-six patients with scar-related VT (age, 50.0 ± 13.7 years and 86.1% men) who underwent VT ablation were reviewed. The automatic rhythmia ultrahigh resolution mapping system was used for electroanatomic substrate mapping. The clinical characteristics and mapping findings, particularly the LAZ characteristics during SR and VT, were analyzed. To determine the association between the LAZ during the SR and VT circuits, the LAZ was defined as five activation patterns: entrance, exit, core, blind alley, and conduction barrier. RESULTS: Forty-five VTs were induced in 36 patients, 91.1% of which were monomorphic. The LAZ of all patients was mapped during the SR and VT circuits, and the consistency of the anatomical locations of the LAZ and VT circuits was analyzed. Using the ultrahigh resolution mapping system, interconversion patterns, including the bridge, T, puzzle, maze, and multilayer types, were identified. VT ablation enabled precise ablation of abnormal late potential conduction channels. CONCLUSION: Five interconversion patterns of the LAZ during the SR and VT circuits were summarized. These findings may help formulate more precise substrate-based ablation strategies for scar-related VT and shorter procedure times.

Relationship between amiodarone response prior to ablation and 1-year outcomes of catheter ablation for atrial fibrillation.

INTRODUCTION: Catheter ablation for atrial fibrillation (AF) is a common therapeutic strategy for patients with either paroxysmal AF (PAF) or persistent AF (persAF), but long-term ablation success rates are imperfect. Maintenance of sinus rhythm immediately before ablation with antiarrhythmic drug (AAD) therapy has been associated with improved outcomes in patients undergoing ablation. Amiodarone has superior efficacy relative to other AADs. Whether failure of amiodarone to maintain sinus rhythm before ablation for either PAF or persAF is associated with poor outcomes is unknown. METHODS: A total of 307 patients who received amiodarone in a 1-year window before undergoing catheter ablation for AF were included. Patients were divided into amiodarone success (n = 183) and amiodarone failure (n = 124) groups based on the response to pre-ablation amiodarone treatment. Analysis of procedural outcomes as a function of response to amiodarone therapy was performed. Patients were followed for at least 12 months postablation, to assess outcomes (adverse events and arrhythmia recurrence). Procedural success was defined by the absence of documented arrhythmia (>30 s) without any antiarrhythmic agents beyond a 90-day blanking period. RESULTS: Following ablation for either PAF or persAF, freedom from any recurrent atrial arrhythmia at 1 year was 57.7% for the entire cohort. One-year freedom from recurrent arrhythmia in the amiodarone success group was comparable to that in the amiodarone failure group (55.7% vs. 60.5%; p = .54). Success rates following ablation did not vary by the response to amiodarone when analyzed for PAF or persAF subgroups. CONCLUSION: Failure to restore and maintain sinus rhythm with amiodarone before ablation for either PAF or persAF is not a predictor of ablation procedural failure. Amiodarone failure alone should not deter practitioners from considering ablation therapy for patients with AF.

Spatial correlation of left atrial low voltage substrate in sinus rhythm versus atrial fibrillation: The rhythm specificity of atrial low voltage substrate.

INTRODUCTION: Improved sinus rhythm (SR) maintenance rates have been achieved in patients with persistent atrial fibrillation (AF) undergoing pulmonary vein isolation plus additional ablation of low voltage substrate (LVS) during SR. However, voltage mapping during SR may be hindered in persistent and long-persistent AF patients by immediate AF recurrence after electrical cardioversion. We assess correlations between LVS extent and location during SR and AF, aiming to identify regional voltage thresholds for rhythm-independent delineation/detection of LVS areas. (1) Identification of voltage dissimilarities between mapping in SR and AF. (2) Identification of regional voltage thresholds that improve cross-rhythm substrate detection. (3) Comparison of LVS between SR and native versus induced AF. METHODS: Forty-one ablation-naive persistent AF patients underwent high-definition (1 mm electrodes; >1200 left atrial (LA) mapping sites per rhythm) voltage mapping in SR and AF. Global and regional voltage thresholds in AF were identified which best match LVS < 0.5 mV and <1.0 mV in SR. Additionally, the correlation between SR-LVS with induced versus native AF-LVS was assessed. RESULTS: Substantial voltage differences (median: 0.52, interquartile range: 0.33-0.69, maximum: 1.19 mV) with a predominance of the posterior/inferior LA wall exist between the rhythms. An AF threshold of 0.34 mV for the entire left atrium provides an accuracy, sensitivity and specificity of 69%, 67%, and 69% to identify SR-LVS < 0.5 mV, respectively. Lower thresholds for the posterior wall (0.27 mV) and inferior wall (0.3 mV) result in higher spatial concordance to SR-LVS (4% and 7% increase). Concordance with SR-LVS was higher for induced AF compared to native AF (area under the curve[AUC]: 0.80 vs. 0.73). AF-LVS < 0.5 mV corresponds to SR-LVS < 0.97 mV (AUC: 0.73). CONCLUSION: Although the proposed region-specific voltage thresholds during AF improve the consistency of LVS identification as determined during SR, the concordance in LVS between SR and AF remains moderate, with larger LVS detection during AF. Voltage-based substrate ablation should preferentially be performed during SR to limit the amount of ablated atrial myocardium.

Conversion to Sinus Rhythm in Refractory Atrial Fibrillation Patients after Atrioventricular Node Ablation with Conduction System Pacing.

Background: "Ablate and pace" strategy is a reasonable treatment option in refractory atrial fibrillation (AF) when sinus rhythm (SR) cannot be achieved with catheter ablation or pharmacological therapy. Atrioventricular node ablation (AVNA) combined with conduction system pacing (CSP), with left bundle branch pacing (LBBP) or His bundle pacing (HBP), is gaining recognition since it offers the most physiological activation of the left ventricle. However, the incidence of conversion to SR after AVNA with CSP is not known. The purpose of the investigation was to determine the incidence of spontaneous conversion to SR and its predicting factors in patients undergoing CSP and AVNA. Methods: Consecutive refractory symptomatic AF patients undergoing AVNA with CSP at our institution between June 2018 and December 2022 were retrospectively analyzed. Twelve lead electrocardiogram (ECG) recordings were analyzed at each outpatient follow-up visit. Echocardiographic and clinical parameters were assessed at baseline and six months after the implantation. Results: Sixty-eight patients (male 42.6%, age 71 ± 8 years, left ventricular ejection fraction 40 ± 15%) were included. Thirty-seven patients (54.4%) received HBP and 31 (45.6%) LBBP. During follow-up, spontaneous conversion to SR was registered in 6 patients (8.8%); 3 in the HBP group and 3 in the LBBP group. Baseline characteristics of patients who converted to SR did not differ from non-sinus rhythm (NSR) patients except for left atrial volume index (LAVI), which was significantly smaller in the SR group (45 mL/ m 2 (41-51) vs. 60 mL/ m 2 (52-75); p = 0.002). Multiple regression model confirmed an inverse association between LAVI and conversion to SR even after considering other clinically relevant covariates (odds ratio 1.273, p = 0.028). At follow-up, LAVI did not change in any group (SR: p = 0.345; NSR: p = 0.508). Improvement in New York Heart Association (NYHA) class was comparable in both groups. Conclusions: Spontaneous conversion to SR after AVNA combined with CSP is not uncommon, especially in patients with smaller left atria. Further studies are warranted to clarify which patients should be considered for initial dual-chamber device implantation to provide atrio-ventricular synchrony in case of SR restoration.

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

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

Techniques improving electrical cardioversion success for patients with atrial fibrillation: a systematic review and meta-analysis.

AIMS: Electrical cardioversion is commonly used to restore sinus rhythm in patients with atrial fibrillation (AF), but procedural technique and clinical success vary. We sought to identify techniques associated with electrical cardioversion success for AF patients. METHODS AND RESULTS: We searched MEDLINE, EMBASE, CENTRAL, and the grey literature from inception to October 2022. We abstracted data on initial and cumulative cardioversion success. We pooled data using random-effects models. From 15 207 citations, we identified 45 randomized trials and 16 observational studies. In randomized trials, biphasic when compared with monophasic waveforms resulted in higher rates of initial [16 trials, risk ratio (RR) 1.71, 95% CI 1.29-2.28] and cumulative success (18 trials, RR 1.10, 95% CI 1.04-1.16). Fixed, high-energy (≥200 J) shocks when compared with escalating energy resulted in a higher rate of initial success (four trials, RR 1.62, 95% CI 1.33-1.98). Manual pressure when compared with no pressure resulted in higher rates of initial (two trials, RR 2.19, 95% CI 1.21-3.95) and cumulative success (two trials, RR 1.19, 95% CI 1.06-1.34). Cardioversion success did not differ significantly for other interventions, including: antero-apical/lateral vs. antero-posterior positioned pads (initial: 11 trials, RR 1.16, 95% CI 0.97-1.39; cumulative: 14 trials, RR 1.01, 95% CI 0.96-1.06); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: four trials, RR 1.11, 95% CI 0.91-1.34; cumulative: four trials, RR 0.98, 95% CI 0.89-1.08) and cathodal vs. anodal configuration (cumulative: two trials, RR 0.99, 95% CI 0.92-1.07). CONCLUSIONS: Biphasic waveforms, high-energy shocks, and manual pressure increase the success of electrical cardioversion for AF. Other interventions, especially pad positioning, require further study.

Premature atrial contractions promote local directional heterogeneities in conduction velocity vectors.

AIMS: Loss of cell-to-cell communication results in local conduction disorders and directional heterogeneity (LDH) in conduction velocity (CV) vectors, which may be unmasked by premature atrial contractions (PACs). We quantified LDH and examined differences between sinus rhythm (SR) and spontaneous PACs in patients with and without atrial fibrillation (AF). METHODS AND RESULTS: Intra-operative epicardial mapping of the right and left atrium (RA, LA), Bachmann's bundle (BB) and pulmonary vein area (PVA) was performed in 228 patients (54 with AF). Conduction velocity vectors were computed at each electrode using discrete velocity vectors. Directions and magnitudes of individual vectors were compared with surrounding vectors to identify LDH. Five hundred and three PACs [2 (1-3) per patient; prematurity index of 45 ± 12%] were included. During SR, most LDH were found at BB and LA [11.9 (8.3-14.9) % and 11.3 (8.0-15.2) %] and CV was lowest at BB [83.5 (72.4-94.3) cm/s, all P < 0.05]. Compared with SR, the largest increase in LDH during PAC was found at BB and PVA [+13.0 (7.7, 18.3) % and +12.5 (10.8, 14.2) %, P < 0.001]; CV decreased particularly at BB, PVA and LA [-10.0 (-13.2, -6.9) cm/s, -9.3 (-12.5, -6.2) cm/s and -9.1 (-11.7, -6.6) cm/s, P < 0.001]. Comparing patients with and without AF, more LDH were found during SR in AF patients at PVA and BB, although the increase in LDH during PACs was similar for all sites. CONCLUSION: Local directional heterogeneity is a novel methodology to quantify local heterogeneity in CV as a possible indicator of electropathology. Intra-operative high-resolution mapping indeed revealed that LDH increased during PACs particularly at BB and PVA. Also, patients with AF already have more LDH during SR, which becomes more pronounced during PACs.