Comparison of Unipolar and Bipolar Voltage Mapping for Localization of Left Atrial Arrhythmogenic Substrate in Patients With Atrial Fibrillation

Background: Presence of left atrial low voltage substrate in bipolar voltage mapping is associated with increased arrhythmia recurrences following pulmonary vein isolation for atrial fibrillation (AF). Besides local myocardial fibrosis, bipolar voltage amplitudes may be influenced by inter-electrode spacing and bipole-to-wavefront-angle. It is unclear to what extent these impact low voltage areas (LVA) in the clinical setting. Alternatively, unipolar electrogram voltage is not affected by these factors but requires advanced filtering. Objectives: To assess the relationship between bipolar and unipolar voltage mapping in sinus rhythm (SR) and AF and identify if the electrogram recording mode affects the quantification and localization of LVA. Methods: Patients (n = 28, 66±7 years, 46% male, 82% persistent AF, 32% redo-procedures) underwent high-density (>1,200 sites, 20 ± 10 sites/cm2, using a 20-pole 2-6-2 mm-spaced Lasso) voltage mapping in SR and AF. Bipolar LVA were defined using four different thresholds described in literature: <0.5 and <1 mV in SR, <0.35 and <0.5 mV in AF. The optimal unipolar voltage threshold resulting in the highest agreement in both unipolar and bipolar mapping modes was determined. The impact of the inter-electrode distance (2 vs. 6 mm) on the correlation was assessed. Regional analysis was performed using an 11-segment left atrial model. Results: Patients had relevant bipolar LVA (23 ± 23 cm$^{2}$ at <0.5 mV in SR and 42 ± 26 cm2 at <0.5 mV in AF). 90 ± 5% (in SR) and 85 ± 5% (AF) of mapped sites were concordantly classified as high or low voltage in both mapping modes. Discordant mapping sites located to the border zone of LVA. Bipolar voltage mapping using 2 vs. 6 mm inter-electrode distances increased the portion of matched mapping points by 4%. The unipolar thresholds (y) which resulted in a high spatial concordance can be calculated from the bipolar threshold (x) using following linear equations: y = 1.06x + 0.26mV (r = 0.994) for SR and y = 1.22x + 0.12mV (r = 0.998) for AF. Conclusion: Bipolar and unipolar voltage maps are highly correlated, in SR and AF. While bipole orientation and inter-electrode spacing are theoretical confounders, their impact is unlikely to be of clinical importance for localization of LVA, when mapping is performed at high density with a 20-polar Lasso catheter

169 Does atrial differences in endothelium damage, leukocyte and platelet activation contribute to chamber specific thrombogenic status in patients with atrial fibrillation?

BackgroundIn atrial fibrillation (AF), the reasons why most of the thrombi form in the left atrium are mainly unknown. In the vasculature, endothelial damage together with platelet activation and inflammation contribute to initiation of blood coagulation and thrombus growth.ObjectiveThe purpose of this study was to investigate whether atrial-specific differences in endothelial damage, leukocyte activation, platelet stimulation occur in patients with AF.MethodsTwenty patients (15 men, 5 women; age 55±8 years, 15 paroxystic AF, 5 persistent AF) with AF undergoing ablation were investigated. Blood samples from the left and right atrium were obtained at the start of the procedure. Procoagulant microparticles (MPs), reliable markers of vascular damage were measured by capture assays. Their procoagulant abilities were quantified by functional prothrombinase assay and their cellular origin were determined (endothelium, platelet, leukocyte). In addition, platelet reactivity was evaluated by whole blood flow cytometry for expression of platelet Pselectin (CD62P), active glycoprotein IIbIIIa receptor (PAC-1). Platelet aggregation was evaluated using Arachidonic acid (AA), ADP, TRAP and collageninduced whole blood aggregometry.ResultsNo atrial-specific differences in the levels of total procoagulant MP, leukocyte-derived-MP and platelet-derived MP could be evidenced. Conversely, endothelial-derived MPs (CD105+) were slightly elevated in the right atrium (RA 0.96±0.53 vs. LA 0.80±0.45nm PhtdSer Eq.; p=0.041). Likewise, collagen-induced platelet aggregation was evidenced in the right atrium (Collagen 1mg/l RA: 48±33% vs LA 37±29%; p 0.035; collagen 2,5mg/l RA: 76±25% vs LA: 60±29%; p=0.001).ConclusionsIn patients with AF, endothelial damage and collageninduced platelet aggregation appear slightly more pronounced in the right atrium. Our data did not substantiate the view that chamber specific enhanced thrombogenic status could be a reliable explanation for the increased propensity for thrombus formation observed in the left atrium in AF patients

An immunodominant La/SSB autoantibody proteome derives from public clonotypes

This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy.The La/SSB autoantigen is a major target of long-term humoral autoimmunity in primary Sjögren’s Syndrome (SS) and systemic lupus erythematosus. A majority of patients with linked anti-Ro60/Ro52/La responses target an NH2-terminal epitope designated LaA that is expressed on Ro/La ribonucleoprotein complexes and the surface membrane of apoptotic cells. In this study, we used high-resolution Orbitrap mass spectrometry to determine the clonality, isotype and V-region sequences of LaA-specific autoantibodies in seven patients with primary SS. Anti-LaA immunoglobulin (Ig)Gs purified from polyclonal sera by epitope-specific affinity chromatography were analysed by combined database and de-novo mass spectrometric sequencing. Autoantibody responses comprised two heavily mutated IgG1 kappa-restricted monoclonal species that were shared (public) across unrelated patients; one clonotype was specified by an IGHV3-30 heavy chain paired with IGKV3-15 light chain and the second by an IGHV3- 43/IGKV3-20 pairing. Shared amino acid replacement mutations were also seen within heavy and light chain complementarity-determining regions, consistent with a common breach of B cell tolerance followed by antigendriven clonal selection. The discovery of public clonotypic autoantibodies directed against an immunodominant epitope on La, taken together with recent findings for the linked Ro52 and Ro60 autoantigens, supports a model of systemic autoimmunity in which humoral responses against protein–RNA complexes are mediated by public sets of autoreactive B cell clonotypes.This work was supported by an Australian National Health and Medical Research Council grant 1041900 to T. P. Gordon and T. K. Chataway

Sinus node disease in subjects with type 1 ECG pattern of Brugada syndrome

AbstractBackgroundThe spectrum of phenotypes related to mutations of the SCN5A gene include Brugada syndrome (BS), long QT syndrome, progressive cardiac conduction defect, and sinus node disease (SND). The present study investigated the incidence of SND in subjects with type 1 electrocardiogram (ECG) pattern of BS.Methods and resultsThe study population consisted of 68 individuals (55 males, mean age 44.8±12.8 years) with spontaneous (n=27) or drug-induced (n=41) type 1 ECG pattern of BS. Twenty-eight subjects were symptomatic with a history of syncope (41.2%). SND was observed in 6 symptomatic subjects (8.8%), and was mainly attributed to sino-atrial block with sinus pauses. Two patients were initially diagnosed with SND, and received a pacemaker. Patients with SND displayed an increased P-wave duration in leads II and V2, PR interval in leads II and V2, QRS duration in leads II and V2, and increased QTc interval in lead V2 (p<0.05). AH and HV intervals as well as corrected sinus node recovery time (cSNRT) were significantly prolonged in subjects with SND (p<0.05). During a mean follow-up period of 5.0±3.6 years, five subjects with a history of syncope suffered appropriate implantable cardioverter defibrillator (ICD) discharges due to ventricular arrhythmias (7.4%). None of those diagnosed with SND suffered syncope or ICD therapies.ConclusionSND is not an uncommon finding in subjects with type 1 ECG pattern of BS. The occurrence of SND in relatively young patients may deserve meticulous investigation including sodium channel blocking test

Online measurement of microembolic signal burden by transcranial doppler during catheter ablation for atrial fibrillation - Results of a multicenter trial

Introduction: Left atrial pulmonary vein isolation (PVI) is an accepted treatment option for patients with symptomatic atrial fibrillation (AF). This procedure can be complicated by stroke or silent cerebral embolism. Online measurement of microembolic signals (MESs) by transcranial Doppler (TCD) may be useful for characterizing thromboembolic burden during PVI. In this prospective multicenter trial, we investigated the burden, characteristics, and composition of MES during left atrial catheter ablation using a variety of catheter technologies. Materials and methods: PVI was performed in a total of 42 patients using the circular-shaped multielectrode pulmonary vein ablation catheter (PVAC) technology in 23, an irrigated radiofrequency (IRF) in 14, and the cryoballoon (CB) technology in 5 patients. TCD was used to detect the total MES burden and sustained thromboembolic showers (TESs) of >30 s. During TES, the site of ablation within the left atrium was registered. MES composition was classified manually into solid, gaseous, or equivocal by off-line expert assessment. Results: The total MES burden was higher when using IRF compared to CB (2,336 +/- 1,654 vs. 593 +/- 231; p = 0.007) and showed a tendency toward a higher burden when using IRF compared to PVAC (2,336 +/- 1,654 vs. 1,685 +/- 2,255; p = 0.08). TES occurred more often when using PVAC compared to IRF (1.5 +/- 2 vs. 0.4 +/- 1.3; p = 0.04) and most frequently when ablation was performed close to the left superior pulmonary vein (LSPV). Of the MES, 17.004 (23%) were characterized as definitely solid, 13.204 (18%) as clearly gaseous, and 44.366 (59%) as equivocal. Discussion: We investigated the burden and characteristics of MES during left atrial catheter ablation for AF. All ablation techniques applied in this study generated a relevant number of MES. There was a significant difference in total MES burden using IRF compared to CB and a tendency toward a higher burden using IRF compared to PVAC. The highest TES burden was found in the PVAC group, particularly during ablation close to the LSPV. The composition of thromboembolic particles was balanced. The impact of MES, TES, and composition of thromboembolic particles on neurological outcome needs to be evaluated further

Machine Learning Using a Single-Lead ECG to Identify Patients With Atrial Fibrillation-Induced Heart Failure

AIMS: Atrial fibrillation (AF) and heart failure often co-exist. Early identification of AF patients at risk for AF-induced heart failure (AF-HF) is desirable to reduce both morbidity and mortality as well as health care costs. We aimed to leverage the characteristics of beat-to-beat-patterns in AF to prospectively discriminate AF patients with and without AF-HF. METHODS: A dataset of 10,234 5-min length RR-interval time series derived from 26 AF-HF patients and 26 control patients was extracted from single-lead Holter-ECGs. A total of 14 features were extracted, and the most informative features were selected. Then, a decision tree classifier with 5-fold cross-validation was trained, validated, and tested on the dataset randomly split. The derived algorithm was then tested on 2,261 5-min segments from six AF-HF and six control patients and validated for various time segments. RESULTS: The algorithm based on the spectral entropy of the RR-intervals, the mean value of the relative RR-interval, and the root mean square of successive differences of the relative RR-interval yielded an accuracy of 73.5%, specificity of 91.4%, sensitivity of 64.7%, and PPV of 87.0% to correctly stratify segments to AF-HF. Considering the majority vote of the segments of each patient, 10/12 patients (83.33%) were correctly classified. CONCLUSION: Beat-to-beat-analysis using a machine learning classifier identifies patients with AF-induced heart failure with clinically relevant diagnostic properties. Application of this algorithm in routine care may improve early identification of patients at risk for AF-induced cardiomyopathy and improve the yield of targeted clinical follow-up

Validating left atrial fractionation and low-voltage substrate during atrial fibrillation and sinus rhythm-A high-density mapping study in persistent atrial fibrillation

Altres ajuts: Deutsche Herzstiftung (German Heart Foundation).Background: Low-voltage-substrate (LVS)-guided ablation for persistent atrial fibrillation (AF) has been described either in sinus rhythm (SR) or AF. Prolonged fractionated potentials (PFPs) may represent arrhythmogenic slow conduction substrate and potentially co-localize with LVS. We assess the spatial correlation of PFP identified in AF (PFP-AF) to those mapped in SR (PFP-SR). We further report the relationship between LVS and PFPs when mapped in AF or SR. Materials and methods: Thirty-eight patients with ablation naïve persistent AF underwent left atrial (LA) high-density mapping in AF and SR prior to catheter ablation. Areas presenting PFP-AF and PFP-SR were annotated during mapping on the LA geometry. Low-voltage areas (LVA) were quantified using a bipolar threshold of 0.5 mV during both AF and SR mapping. Concordance of fractionated potentials (CFP) (defined as the presence of PFPs in both rhythms within a radius of 6 mm) was quantified. Spatial distribution and correlation of PFP and CFP with LVA were assessed. The predictors for CFP were determined. Results: PFPs displayed low voltages both during AF (median 0.30 mV (Q1-Q3: 0.20-0.50 mV) and SR (median 0.35 mV (Q1-Q3: 0.20-0.56 mV). The duration of PFP-SR was measured at 61 ms (Q1-Q3: 51-76 ms). During SR, most PFP-SRs (89.4 and 97.2%) were located within LVA (40%), followed by posterior LA (>20%) and septal LA (>15%). The extent of LVA 80%) fractionation concordance in AF and SR. Conclusion: Substrate mapping in SR vs. AF reveals smaller areas of low voltage and fewer sites with PFP. PFP-SR are located within low-voltage areas in SR. There is a high degree of spatial agreement (80%) between PFP-AF and PFP-SR in patients with moderate LVA in SR (>16% of LA surface). These findings should be considered when substrate-based ablation strategies are applied in patients with the left atrial low-voltage substrate with recurrent persistent AF

Structural and electrophysiological determinants of atrial cardiomyopathy identify remodeling discrepancies between paroxysmal and persistent atrial fibrillation

Background: Progressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency. Methods: Consecutive patients with paroxysmal (n = 134) or persistent (n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency. Results: In training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area < 1.0 mV (threshold 4.55 cm$^2$) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC < 0.60 in identifying individuals with persistent AF in current study. Conclusion: Among 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF

Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation. Radiofrequency ablation is the most common method, and cryoballoon ablation is the second most frequently used technology. METHODS: We conducted a multicenter, randomized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation. The primary efficacy end point in a time-to-event analysis was the first documented clinical failure (recurrence of atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of antiarrhythmic drugs, or repeat ablation) following a 90-day period after the index ablation. The noninferiority margin was prespecified as a hazard ratio of 1.43. The primary safety end point was a composite of death, cerebrovascular events, or serious treatment-related adverse events. RESULTS: A total of 762 patients underwent randomization (378 assigned to cryoballoon ablation and 384 assigned to radiofrequency ablation). The mean duration of follow-up was 1.5 years. The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 34.6% and 35.9%, respectively; hazard ratio, 0.96; 95% confidence interval [CI], 0.76 to 1.22; P<0.001 for noninferiority). The primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 10.2% and 12.8%, respectively; hazard ratio, 0.78; 95% CI, 0.52 to 1.18; P=0.24). CONCLUSIONS: In this randomized trial, cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, and there was no significant difference between the two methods with regard to overall safety. (Funded by Medtronic; FIRE AND ICE ClinicalTrials.gov number, NCT01490814.)