Electrogram Fractionation Research Articles

Ultra-high density mapping and ablation of localized microreentrant tachycardias: insight from the CHARISMA registry

Abstract Background The optimal criteria for distinguishing microreentrant atrial tachycardias (mAT) from macroreentrant atrial arrhythmias (MAT) in clinical practice have not been definitively established. Recent advancements in ultra-high-density mapping featuring automated functionalities, has enhanced our understanding of mAT circuits and the precise localization of foci. Purpose Our intent was to observe the diagnostic support provided by high density mapping and Lumipoint algorithm in mAT as well as the ablation outcomes. Methods Consecutive patients eligible for atrial tachycardia (AT) ablation in 22 Italian centres were prospectively enrolled. all ATs were comprehensively mapped in either the left or right atrium utilizing the Rhythmia mapping system and the 64-pole Orion basket catheter. A mAT was defined as an AT characterized by slow, continuous, low fragmented potentials covering a minimum of 50% of the tachycardia cycle length (CL) within a confined area (defined as a circuit within < 1 cm2), enclosed by a couple of closed splines of the Orion catheter, and exhibiting a centrifugal activation pattern to the rest of the atria. The Lumipoint tool was systematically employed to confirm electrogram fragmentation within this defined area. Results Among 159 ATs analysed, 97 (61.0%) were identified as MAT, 50 (31.4%) as focal atrial tachycardias and 12 (7.5%) as mAT. Of these latter, 6 patients (50%) had a previous history of atrial ablation procedure. Concerning the mAT group, the predominant origin site was the left atrium (10 mAT, 83,3%); the targeted activity was localized in the anterior wall in 4 cases (33.3%), in proximity to PVs in 3 cases (25%), along the left ridge in 2 cases (16.6%) and at the roof in 1 case (8,3%). In the remaining right mAT, the foci were found in the free wall and along the CTI in 1 case (8.3% each). The electrical activity spanning the whole CL was detected by 2.7±1.8 pairs of close bipoles of the Orion catheter, was confined to a region of 0.36±0.3cm2 with the longest component of fractionated EGM per spline equal to 64.7±17% of the CL. Low voltage areas (<0.1 mV) were detected in all mAT cases and colocalized with the origin site. Voltage level was 0.2±0.1mV at the site of longest duration of the fragmented potential. A single shot RF delivery terminated each arrhythmia at targeted location. Consolidative RF ablations were then delivered in the adjacent area. Over a median of 288 [248-349] days of follow-up, 5 (3.1%) patients suffered from an AT/AF arrhythmia recurrence and of these, 3 (3.1%) were in the MAT group, 1 (2%) in the focal AT and 1 (8.3%) in the mAT group. No complications were observed. Conclusions A novel automated algorithm for microreentrant atrial tachycardia identification, coupled with the identification of matched areas of electrogram fractionation by the Orion catheter, may restrict the extent of required ablation and result in a low arrhythmia recurrence.

Quantitative analysis of fractionated electrogram area of left atrium during right atrial pacing as an indicator of left atrial electrical remodeling in patients with atrial fibrillation.

The clinical significance of left atrial local electrogram fractionation after restoration of sinus rhythm in patients with atrial fibrillation (AF) has not been elucidated. We evaluated ultrahigh-resolution maps of the left atrium (LA) during RA pacing acquired after pulmonary vein isolation in 40 patients with AF. The association between low-voltage area (LVA, <0.5 mV), fractionated electrogram area (FEA, the highlighted area with LUMIPOINT™ Complex Activation), the interval from onset of LA activation to wavefront collision at the mitral isthmus (LA activation time), and wave propagation velocity (WPV) was evaluated quantitatively. The total LVA, total FEA with ≥5.0 peaks or ≥7.0 peaks were 7.0 ± 7.9 cm2, 15.9 ± 12.9 cm2, and 5.2 ± 7.5 cm2, respectively. These areas were predominantly observed in the anteroseptal region. Total LVA, total FEA with ≥5.0 peaks, and total FEA with ≥5.0 peaks in the normal voltage area (NVA: ≥0.5 mV) correlated with LA activation time (R = 0.69, 0.75, and 0.71; each p < .0001). In the anterior wall, these areas correlated with regional mean WPV (R = -0.75, -0.83, and - 0.55; each p < .0001) and the extent of slow conduction area (SCA) with WPV <0.3 m/s (R = 0.89, 0.84, 0.33; p < .0001 for LVA and FEA, p < .05 for FEA located in NVA). The anterior wall FEA with ≥7.0 peaks and that in the NVA showed a better correlation in predicting anterior wall SCA (R = 0.92 and 0.86, each p < .0001). Quantitative analysis of FEA together with LVA may facilitate the assessment of LA electrical remodeling.

Electro-Mechanical Alterations in Atrial Fibrillation: Structural, Electrical, and Functional Correlates.

Atrial fibrillation is the most common arrhythmia encountered in clinical practice affecting both patients' survival and well-being. Apart from aging, many cardiovascular risk factors may cause structural remodeling of the atrial myocardium leading to atrial fibrillation development. Structural remodelling refers to the development of atrial fibrosis, as well as to alterations in atrial size and cellular ultrastructure. The latter includes myolysis, the development of glycogen accumulation, altered Connexin expression, subcellular changes, and sinus rhythm alterations. The structural remodeling of the atrial myocardium is commonly associated with the presence of interatrial block. On the other hand, prolongation of the interatrial conduction time is encountered when atrial pressure is acutely increased. Electrical correlates of conduction disturbances include alterations in P wave parameters, such as partial or advanced interatrial block, alterations in P wave axis, voltage, area, morphology, or abnormal electrophysiological characteristics, such as alterations in bipolar or unipolar voltage mapping, electrogram fractionation, endo-epicardial asynchrony of the atrial wall, or slower cardiac conduction velocity. Functional correlates of conduction disturbances may incorporate alterations in left atrial diameter, volume, or strain. Echocardiography or cardiac magnetic resonance imaging (MRI) is commonly used to assess these parameters. Finally, the echocardiography-derived total atrial conduction time (PA-TDI duration) may reflect both atrial electrical and structural alterations.

Detectable reentrant circuits in localized microreentrant tachycardias in the era of ultra high-density mapping

Abstract Funding Acknowledgements Type of funding sources: None. Background Optimal criteria in clinical practice differentiating microreentrant atrial tachycardias (mAT) from macroreentrant atrial arrhythmias (MAT) have not yet been clarified. The use of multielectrode catheters and the recent development of ultra high-density mapping (UHDM) with automated features has improved our knowledge of mAT circuits and foci location. Purpose In the present study, we systematically evaluated AT mechanisms in a large consecutive cohort of patients with MAT identifying the precise mAT circuits using the Rhythmia mapping system. Methods Consecutive patients indicated for MAT ablation from January 2021 to November 2021 at 33 centers were prospectively included. All MATs were completely mapped in the left or right atrium by means of the Rhythmia mapping system and the 64-poles Orion basket catheter. For study purpose, a mAT was defined as an AT with slow continuous low fragmented potentials covering at least 50% of tachycardia cycle length (CL) in a small area (set as a circuit within &amp;lt; 1 cm2) and in a couple of closed splines of the Orion catheter and a centrifugal activation pattern to the remainder of the atria. The Lumipoint tool was systematically used to confirm EGM fragmentation inside this area. Data are reported as mean±SD. Results One-hundred eighty-seven MATs were analyzed: 100 (53.7%) atypical left atrial flutter, 27 (14.3%) left AT and 60 (32%) right AT. A total of 7 MAT (prevalence of 3.7%) was identified as mATs (6 atypical left atrial flutter and 1 AT), with 5 out 7 with a previous history of AF ablation procedure. The percentage of atrial surface with a voltage level below 0.1 mV was 19±17%. The CL was 329±78ms. The electrical activity spanning the whole CL was detected by 2±0.6 pairs of close bipoles of the Orion catheter, and was actually confined to a region of 0.4±0.2cm2 with continuous highly fractionated potential covering 68±10% of the CL (longest component of fractionated EGM per spline=74±18% of the CL). Voltage level was 0.3±0.1mV at RF delivery site and 0.2±0.1mV at the site of longest duration of the fragmented potential, respectively. Targeted mAT activity was identified closer to PVs in three cases and at the mid portion of the anterior wall and at the roof in two cases each, respectively. In all cases a single shot RF delivery terminated each arrhythmia at targeted location. Consolidative RF ablations were then delivered in the adjacent area. No complication occurred. At three months follow-up all patients remained free from any AT recurrence. Conclusions In this standard of care clinical experience with UHDM system, the prevalence of mAT seems to be higher than previously reported in literature. A technique based on mAT identification through a novel automated algorithm and matched area of electrogram fractionation captured by the Orion catheter may limit the extent of ablation needed.

Electrogram fractionation during sinus rhythm occurs in normal voltage atrial tissue in patients with atrial fibrillation.

Electrogram (EGM) fractionation is often associated with diseased atrial tissue; however, mechanisms for fractionation occurring above an established threshold of 0.5mV have never been characterized. We sought to investigate during sinus rhythm (SR) the mechanisms underlying bipolar EGM fractionation with high-density mapping in patients with atrial fibrillation (AF). Forty-five patients undergoing AF ablation (73% paroxysmal, 27% persistent) were mapped at high density (18562±2551 points) during SR (Rhythmia). Only bipolar EGMs with voltages above 0.5mV were considered for analysis. When fractionation (>40ms and >4 deflections) was detected, we classified the mechanisms as slow conduction, wave-front collision, or a pivot point. The relationship between EGM duration and amplitude, and tissue anisotropy and slow conduction, was then studied using a computational model. Of the 45 left atria analyzed, 133 sites of EGM fragmentation were identified with voltages above 0.5mV. The most frequent mechanism (64%) was slow conduction (velocity 0.45m/s±0.2) with mean EGM voltage of 1.1±0.5mV and duration of 54.9±9.4ms. Wavefront collision was the second most frequent (19%), characterized by higher voltage (1.6±0.9mV) and shorter duration (51.3±11.3ms). Pivot points (9%) were associated with the highest degree of fractionation with 70.7±6.6ms and 1.8±1mV. In 10 sites (8%) fractionation was unexplained. The EGM duration was significantly different among the 3 mechanisms (p=.0351). In patients with a history of AF, EGM fractionation can occur at amplitudes>0.5mV when in SR in areas often considered not to be diseased tissue. The main mechanism of EGM fractionation is slow conduction, followed by wavefront collision and pivot sites.

New insights into risk stratification of Brugada syndrome from high density epicardial electroanatomic mapping

Abstract Background/Introduction Brugada syndrome (BrS) has been initially described as a channelopathy with no structural heart disease but a growing body of evidence points towards structural anomalies in the epicardium of right ventricle outflow tract (RVOT-EPI). Since its first description the electrical substrate of BrS has been thought to be a fractionation of the electrograms (EGMs) in the RVOT-EPI. Also there is recent evidence that SCN5A mutation BrS patients might be at increased risk of sudden cardiac death (SCD). No studies correlated high-density mapping substrate with clinical outcomes. Purpose The aim of the current study was to compare clinical characteristics of BRS patients with EGMs characteristics from high-density epicardial mapping with Advisor HD-Grid mapping catheter. Methods All consecutive patients with BrS who underwent hybrid RVOT-EPI substrate ablation at our University Hospital between April 2018 and March 2021 were retrospectively included in the study. Genetic analysis was performed in all patients and clinical data were collected. BrS was diagnosed following current recommendations. Inclusion criteria were: 1) use of Advisor HD-Grid mapping catheter and 3D-electroanatomical (EAM) mapping system EnSite Precision; 2) acquisition of EAM before and after ajmaline infusion at standard protocol (1 mg/kg in 5 minutes). Bipolar EGMs were considered abnormal (aEGMs) if they met at least 1 of the following: prolonged duration (&amp;gt;80 ms), fragmented components (at least 2 distinct peaks), and/or late potentials extending beyond the end of the QRS complex. aEGMs duration (Ed) was defined as the time from surface QRS onset in D2 to bipolar EGM offset. Results Fifteen patients were included in the study. Six patients (40%) had history of SCD or inducible ventricular arrhythmias (VAs) at electrophysiological study and 5 patients (33.3%) had a mutation of SCN5A. The mean number of points of EAMs was 1020±500. Patients with history of SCD or VAs compared with patients without history had similar Ed before ajmaline [117.5 ms (100.6–132.5) vs 110.5 ms (106.8–114.8), p=0.72] but longer Ed after ajmaline [247.5 ms (231.6–273.9) vs 188.0 ms (178.0, 211.5), p=0.034]. The best cutoff of Ed after ajmaline to predict VAs history was 233 msec (AUC of the model 0.83, sensitivity: 0.98, specificity: 0.66). Patients with SCN5A mutation compared with patients without had similar Ed before ajmaline [125.2 ms (117.9–132.6) vs 105.0 ms (103.0–119.0), p=0.24] but longer Ed after ajmaline [270.0 ms (259.0–280.5) vs 200.8 ms (181.2–224.2), p=0.037], figure 1. The best cutoff of Ed after ajmaline to predict SCN5A mutation was 256.5 ms (AUC of the model 0.84, sensitivity: 0.80, specificity: 0.98), figure 2. Conclusions High density RVOT epicardial mapping provides data of clinical meaning in risk stratification of BrS patients. These data should be interpreted in the context of a population undergone RVOT-EPI substrate ablation. Funding Acknowledgement Type of funding sources: None. aEGM duration and SCD/VA or SCN5AROC curves for EGM derived prediction

Detection of Endo-epicardial Asynchrony in the Atrial Wall Using One-Sided Unipolar and Bipolar Electrograms

Endo-epicardial asynchrony (EEA) is a new mechanism possibly maintaining atrial fibrillation. We aimed to determine the sensitivity and best recording modus to detect EEA on electrograms recorded from one atrial side using electrogram fractionation. Simultaneously obtained right atrial endo- and epicardial electrograms from 22 patients demonstrating EEA were selected. Unipolar and (converted) bipolar electrograms were analyzed for presence and characteristics of fractionation corresponding to EEA. Sensitivity of presence of EEA corresponding fractionation was high in patients (86–96%) and moderately high (65–78%) for the asynchronous surface area for unipolar and bipolar electrograms equally. In bipolar electrograms, signal-to-noise ratio of EEA corresponding fractionation decreased and additional fractionation increased for electrograms recorded at the endocardium. Sensitivity of fractionation corresponding to EEA is high for both unipolar and bipolar electrograms. Unipolar electrograms are more suited for detection of EEA due to a larger signal-to-noise ratio and less disturbance of additional fractionation.Graphical Unipolar electrograms are more suited than bipolar electrograms to detect endo-epicardial asynchrony on one side of the atrial wall using electrogram fractionation.

Assessing the ability of substrate mapping techniques to guide ventricular tachycardia ablation using computational modelling

BackgroundIdentification of targets for ablation of post-infarction ventricular tachycardias (VTs) remains challenging, often requiring arrhythmia induction to delineate the reentrant circuit. This carries a risk for the patient and may not be feasible. Substrate mapping has emerged as a safer strategy to uncover arrhythmogenic regions. However, VT recurrence remains common. GoalTo use computer simulations to assess the ability of different substrate mapping approaches to identify VT exit sites. MethodsA 3D computational model of the porcine post-infarction heart was constructed to simulate VT and paced rhythm. Electroanatomical maps were constructed based on endocardial electrogram features and the reentry vulnerability index (RVI - a metric combining activation (AT) and repolarization timings to identify tissue susceptibility to reentry). Since scar transmurality in our model was not homogeneous, parameters derived from all signals (including dense scar regions) were used in the analysis. Potential ablation targets obtained from each electroanatomical map during pacing were compared to the exit site detected during VT mapping. ResultsSimulation data showed that voltage cut-offs applied to bipolar electrograms could delineate the scar, but not the VT circuit. Electrogram fractionation had the highest correlation with scar transmurality. The RVI identified regions closest to VT exit site but was outperformed by AT gradients combined with voltage cut-offs. The performance of all metrics was affected by pacing location. ConclusionsSubstrate mapping could provide information about the infarct, but the directional dependency on activation should be considered. Activation-repolarization metrics have utility in safely identifying VT targets, even with non-transmural scars.

Epicardial Adipose Tissue Accumulation Confers Atrial Conduction Abnormality

BackgroundClinical studies have reported that epicardial adipose tissue (EpAT) accumulation associates with the progression of atrial fibrillation (AF) pathology and adversely affects AF management. The role of local cardiac EpAT deposition in disease progression is unclear, and the electrophysiological, cellular, and molecular mechanisms involved remain poorly defined. ObjectivesThe purpose of this study was to identify the underlying mechanisms by which EpAT influences the atrial substrate for AF. MethodsPatients without AF undergoing coronary artery bypass surgery were recruited. Computed tomography and high-density epicardial electrophysiological mapping of the anterior right atrium were utilized to quantify EpAT volumes and to assess association with the electrophysiological substrate in situ. Excised right atrial appendages were analyzed histologically to characterize EpAT infiltration, fibrosis, and gap junction localization. Co-culture experiments were used to evaluate the paracrine effects of EpAT on cardiomyocyte electrophysiology. Proteomic analyses were applied to identify molecular mediators of cellular electrophysiological disturbance. ResultsHigher local EpAT volume clinically correlated with slowed conduction, greater electrogram fractionation, increased fibrosis, and lateralization of cardiomyocyte connexin-40. In addition, atrial conduction heterogeneity was increased with more extensive myocardial EpAT infiltration. Cardiomyocyte culture studies using multielectrode arrays showed that cardiac adipose tissue-secreted factors slowed conduction velocity and contained proteins with capacity to disrupt intermyocyte electromechanical integrity. ConclusionsThese findings indicate that atrial pathophysiology is critically dependent on local EpAT accumulation and infiltration. In addition to myocardial architecture disruption, this effect can be attributed to an EpAT-cardiomyocyte paracrine axis. The focal adhesion group proteins are identified as new disease candidates potentially contributing to arrhythmogenic atrial substrate.

Endocardial-Epicardial Phase Mapping of Prolonged Persistent Atrial Fibrillation Recordings: High Prevalence of Dissociated Activation Patterns.

Endocardial-epicardial dissociation and focal breakthroughs in humans with atrial fibrillation (AF) have been recently demonstrated using activation mapping of short 10-second AF segments. In the current study, we used simultaneous endo-epi phase mapping to characterize endo-epi activation patterns on long segments of human persistent AF. Simultaneous intraoperative mapping of endo- and epicardial lateral right atrium wall was performed in patients with persistent AF using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms of continuous 2-minute AF recordings and electrodes locations were exported for phase analyses. We defined endocardial-epicardial dissociation as phase difference of ≥20 ms between paired endo-epi electrodes. Wavefronts were classified as rotations, single wavefronts, focal waves, or disorganized activity as per standard criteria. Endo-Epi wavefront patterns were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with ≥5 directional changes occupying at least 70% of sample duration. Fourteen patients with persistent AF undergoing cardiac surgery were included. Endocardial-epicardial dissociation was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (Endo: 41.3% versus Epi: 46.8%, P=0.0194) and single wavefronts (Endo: 31.3% versus Epi: 28.1%, P=0.129) were the dominant patterns. Transient rotations (Endo: 22% versus Epi: 19.2%, P=0.169; mean duration: 590±140 ms) and nonsustained focal waves (Endo: 1.2% versus Epi: 1.6%, P=0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. Electrogram fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P<0.0001). Simultaneous endo-epi phase mapping of prolonged human persistent AF recordings shows significant Endocardial-epicardial dissociation marked temporal heterogeneity, discordant and transitioning wavefronts patterns and complex fractionations. No sustained focal activity was observed. Such complex 3-dimensional interactions provide insight into why endocardial mapping alone may not fully characterize the AF mechanism and why endocardial ablation may not be sufficient. Graphic Abstract: A graphic abstract is available for this article.

Short-Time Estimation of Fractionation in Atrial Fibrillation with Coarse-Grained Correlation Dimension for Mapping the Atrial Substrate.

Atrial fibrillation (AF) is currently the most common cardiac arrhythmia, with catheter ablation (CA) of the pulmonary veins (PV) being its first line therapy. Ablation of complex fractionated atrial electrograms (CFAEs) outside the PVs has demonstrated improved long-term results, but their identification requires a reliable electrogram (EGM) fractionation estimator. This study proposes a technique aimed to assist CA procedures under real-time settings. The method has been tested on three groups of recordings: Group 1 consisted of 24 highly representative EGMs, eight of each belonging to a different AF Type. Group 2 contained the entire dataset of 119 EGMs, whereas Group 3 contained 20 pseudo-real EGMs of the special Type IV AF. Coarse-grained correlation dimension (CGCD) was computed at epochs of 1 s duration, obtaining a classification accuracy of 100% in Group 1 and 84.0–85.7% in Group 2, using 10-fold cross-validation. The receiver operating characteristics (ROC) analysis for highly fractionated EGMs, showed 100% specificity and sensitivity in Group 1 and 87.5% specificity and 93.6% sensitivity in Group 2. In addition, 100% of the pseudo-real EGMs were correctly identified as Type IV AF. This method can consistently express the fractionation level of AF EGMs and provides better performance than previous works. Its ability to compute fractionation in short-time can agilely detect sudden changes of AF Types and could be used for mapping the atrial substrate, thus assisting CA procedures under real-time settings for atrial substrate modification.

Association of Left Atrial High-Resolution Late Gadolinium Enhancement on Cardiac Magnetic Resonance With Electrogram Abnormalities Beyond Voltage in Patients With Atrial Fibrillation.

Conflicting data have been reported on the association of left atrial (LA) late gadolinium enhancement (LGE) with atrial voltage in patients with atrial fibrillation. The association of LGE with electrogram fractionation and delay remains to be examined. We sought to examine the association between LA LGE on cardiac magnetic resonance and electrogram abnormalities in patients with atrial fibrillation. High-resolution LGE cardiac magnetic resonance was performed before electrogram mapping and ablation in atrial fibrillation patients. Cardiac magnetic resonance features were quantified using LA myocardial signal intensity Z score (SI-Z), a continuous normalized variable, as well as a dichotomous LGE variable based on previously validated methodology. Electrogram mapping was performed pre-ablation during sinus rhythm or LA pacing, and electrogram locations were coregistered with cardiac magnetic resonance images. Analyses were performed using multilevel patient-clustered mixed-effects regression models. In the 40 patients with atrial fibrillation (age, 63.2±9.2 years; 1312.3±767.3 electrogram points per patient), lower bipolar voltage was associated with higher SI-Z in patients who had undergone previous ablation (coefficient, -0.049; P<0.001) but not in ablation-naive patients (coefficient, -0.004; P=0.7). LA electrogram activation delay was associated with SI-Z in patients with previous ablation (SI-Z: coefficient, 0.004; P<0.001 and LGE: coefficient, 0.04; P<0.001) but not in ablation-naive patients. In contrast, increased LA electrogram fractionation was associated with SI-Z (coefficient, 0.012; P=0.03) and LGE (coefficient, 0.035; P<0.001) only in ablation-naive patients. The association of LA LGE with voltage is modified by ablation. Importantly, in ablation-naive patients, atrial LGE is associated with electrogram fractionation even in the absence of voltage abnormalities.

Region-specific parasympathetic nerve remodeling in the left atrium contributes to creation of a vulnerable substrate for atrial fibrillation.

Atrial fibrillation (AF) is the most common heart rhythm disorder and a major cause of stroke. Unfortunately, current therapies for AF are suboptimal, largely because the molecular mechanisms underlying AF are poorly understood. Since the autonomic nervous system is thought to increase vulnerability to AF, we used a rapid atrial pacing (RAP) canine model to investigate the anatomic and electrophysiological characteristics of autonomic remodeling in different regions of the left atrium. RAP led to marked hypertrophy of parent nerve bundles in the posterior left atrium (PLA), resulting in a global increase in parasympathetic and sympathetic innervation throughout the left atrium. Parasympathetic fibers were more heterogeneously distributed in the PLA when compared with other left atrial regions; this led to greater fractionation and disorganization of AF electrograms in the PLA. Computational modeling revealed that heterogeneously distributed parasympathetic activity exacerbates sympathetic substrate for wave break and reentry. We further discovered that levels of nerve growth factor (NGF) were greatest in the left atrial appendage (LAA), where AF was most organized. Preferential NGF release by the LAA - likely a direct function of frequency and regularity of atrial stimulation - may have important implications for creation of a vulnerable AF substrate.

Kolmogorov Complexity of Coronary Sinus Atrial Electrograms before Ablation Predicts Termination of Atrial Fibrillation after Pulmonary Vein Isolation

Atrial fibrillation (AF) is related to a very complex local electrical activity reflected in the rich morphology of intracardiac electrograms. The link between electrogram complexity and efficacy of the catheter ablation is unclear. We test the hypothesis that the Kolmogorov complexity of a single atrial bipolar electrogram recorded during AF within the coronary sinus (CS) at the beginning of the catheter ablation may predict AF termination directly after pulmonary vein isolation (PVI). The study population consisted of 26 patients for whom 30 s baseline electrograms were recorded. In all cases PVI was performed. If AF persisted after PVI, ablation was extended beyond PVs. Kolmogorov complexity estimated by Lempel–Ziv complexity and the block decomposition method was calculated and compared with other measures: Shannon entropy, AF cycle length, dominant frequency, regularity, organization index, electrogram fractionation, sample entropy and wave morphology similarity index. A 5 s window length was chosen as optimal in calculations. There was a significant difference in Kolmogorov complexity between patients with AF termination directly after PVI compared to patients undergoing additional ablation (p < 0.01). No such difference was seen for remaining complexity parameters. Kolmogorov complexity of CS electrograms measured at baseline before PVI can predict self-termination of AF directly after PVI.

P1234Weight fluctuation demonstrates residual atrial arrhythmogenic substrate despite final weight loss in a chronic sheep model: implications for epicardial fat and fibrofatty infiltrates

Abstract Background Obesity-mediated epicardial adipose tissue (EAT) expansion drives fat cell infiltration which forms the unique substrate for atrial fibrillation (AF). The LEGACY study showed the benefits of weight loss but an attenuated response with weight fluctuation. How fluxes in weight impacts the atrial substrate in not known. Objective To investigate EAT and the atrial substrates due to weight fluctuation, with comparison to stable obesity. Methods We studied 24 sheep in 3 equal groups over 80 weeks: 1. Obesity induced by high calorie diet fed ad libitum; 2. Weight fluctuation induced by 20-week cycle of weight gain/loss (20:20:20:20); and 3. Lean controls fed quality hay to maintain baseline weight. All sheep underwent: daily weight measurement; haemodynamic and imaging assessments (cardiac MRI; dual-energy X-ray absorptiometry; and matrix assisted laser desorption infrared lipid imaging); electrophysiological studies and electroanatomic mapping; histological and structural analysis. Evaluations included: atrial voltage, conduction velocity, and refractoriness (7 sites, 2 cycle lengths), electrogram fractionation, EAT volume, fibro-fatty infiltration, myolysis of myocytes, and spatial distribution of intra-atrial lipids. Results The Table shows the group differences. Compared to reference controls, obesity demonstrated: Increased atrial volume and pressure, abnormal atrial electrical properties, expanded EAT and ensuing fibro-fatty infiltrations, and myolysis of myocytes. Despite comparable weight and EAT with controls, weight fluctuation resulted in extensive and severe fibro-fatty infiltrations, and twofold greater myolysis that persisted. Moreover, characteristic profiles and abundance of lipid species in the atrial myocardium were noted on further evaluation. More importantly, EAT and fibro-fatty infiltrates strongly correlated with increased atrial volume and pressure; with only fibro-fatty infiltrates correlating with fractionated electrograms (r=0.71, p&lt;0.001) and conduction slowing (r=−0.59, p=0.006). Similarly, atrial myolysis exhibited significant correlations with atrial enlargement and haemodynamics, and electrical substrates (p&lt;0.05 for all). Conclusions Obesity induces fibro-fatty replacement of atrial myocytes and deterioration of contractile units, which may drive impaired electrical remodeling. Despite final weight loss, weight fluctuation demonstrates residual electro-structural, fibro-fatty and contractile substrates.

Electroanatomical Remodeling oftheAtria in Obesity: Impact of Adjacent Epicardial Fat.

The aims of the study were to characterize: 1) electrical and electroanatomical remodeling in patients with atrial fibrillation (AF) with obesity; and 2) the impact of epicardial fat depots on adjacent atrial tissue. Obesity is associated with an increased risk of AF. A total of 115 patients with AF who underwent AF ablation were screened. After exclusion, 26 patients were divided into 2 groups (obese: body mass index [BMI]≥27 kg/m2 and reference: BMI<27 kg/m2). They underwent cardiac magnetic resonance (CMR) imaging and electroanatomic mapping of the left atrium (LA) in sinus rhythm before AF ablation. Atrial and ventricular epicardial adipose tissue (EAT) were assessed by CMR. The following electrophysiological parameters were assessed: global and regional voltage, conduction velocity (CV), electrogram fractionation, and CV heterogeneity. In addition, the regional relationship between LA EAT depots and the electrophysiological substrate was evaluated. The BMIs of the obese and reference groups were 30.2 ± 2.6 and 25.2 ± 1.3 kg/m2, respectively (p< 0.001). There was no difference in the left ventricular ejection fraction and a nonsignificant increase in LA size with obesity. Obesity was associated with increase in all measures of EAT (p< 0.05), with a predominant distribution adjacent to the posterior LA and the atrioventricular groove. Obesity was associated with reduced global CV (0.86 ± 0.31 m/s vs. 1.26 ± 0.29 m/s; p< 0.001), with a nonsignificant increase in conduction heterogeneity (p= 0.10), increased fractionation (54 ± 17% vs. 25 ± 10%; p< 0.001), and regional alteration in voltage (p< 0.001). Although the global LA voltage was preserved, there was greater voltage heterogeneity (p= 0.001) and increased low-voltage areas (13.9% vs. 3.4%; p< 0.001) in the obese group compared with the reference group. The low voltage areas were predominantly seen in the posterior and/or inferior LA, which was similar to location of EAT on CMR imaging. Among various measures of obesity, LA EAT volume correlated best with posterior LA fractionation (r2= 0.55 for LA EAT volume vs. r2= 0.36 for BMI) and CV (r2= 0.31 for LA EAT volume vs. r2= 0.22 for BMI). Obesity is associated with electroanatomical remodeling of the atria, with areas of low voltage, conduction slowing, and greater fractionation of electrograms. These changes were more pronounced in regions adjacent to epicardial fat depots, which suggested a role for fat depots in the development of the AF substrate.

Unipolar atrial electrogram morphology from an epicardial and endocardial perspective

Endo-epicardial asynchrony (EEA) and the interplay between the endocardial and epicardial layers could be important in the pathophysiology of atrial arrhythmias. The morphologic differences between epicardial and endocardial atrial electrograms have not yet been described, and electrogram morphology may hold information about the presence of EEA. The purpose of this study was to directly compare epicardial to endocardial unipolar electrogram morphology during sinus rhythm (SR) and to evaluate whether EEA contributes to electrogram fractionation by correlating fractionation to spatial activation patterns. In 26 patients undergoing cardiac surgery, unipolar electrograms were simultaneously recorded from the epicardium and endocardium at the inferior, middle, and superior right atrial (RA) free wall during SR. Potentials were analyzed for epi-endocardial differences in local activation time, voltage, RS ratio, and fractionation. The surrounding and opposite electrograms of fractionated deflections were evaluated for corresponding local activation times in order to determine whether fractionation originated from EEA. The superior RA was predisposed to delayed activation, EEA, and fractionation. Both epicardial and endocardial electrograms demonstrated an S-predominance. Fractionation was mostly similar between the 2 sides; however, incidentally deflections up to 4 mV on 1 side could be absent on the other side. Remote activation was responsible for most fractionated deflections (95%) in SR, of which 4% could be attributed to EEA. Local epi-endocardial differences in electrogram fractionation occur occasionally during SR but will likely increase during arrhythmias due to increasing EEA and (functional) conduction disorders. Electrogram fractionation can originate from EEA, and this study demonstrated that unipolar electrogram fractionation can potentially identify EEA.

In This Issue: November

In This Issue: November

Atrial Electrogram Fractionation Distribution before and after Pulmonary Vein Isolation in Human Persistent Atrial Fibrillation-A Retrospective Multivariate Statistical Analysis.

Purpose: Complex fractionated atrial electrograms (CFAE)-guided ablation after pulmonary vein isolation (PVI) has been used for persistent atrial fibrillation (persAF) therapy. This strategy has shown suboptimal outcomes due to, among other factors, undetected changes in the atrial tissue following PVI. In the present work, we investigate CFAE distribution before and after PVI in patients with persAF using a multivariate statistical model.Methods: 207 pairs of atrial electrograms (AEGs) were collected before and after PVI respectively, from corresponding LA regions in 18 persAF patients. Twelve attributes were measured from the AEGs, before and after PVI. Statistical models based on multivariate analysis of variance (MANOVA) and linear discriminant analysis (LDA) have been used to characterize the atrial regions and AEGs.Results: PVI significantly reduced CFAEs in the LA (70 vs. 40%; P < 0.0001). Four types of LA regions were identified, based on the AEGs characteristics: (i) fractionated before PVI that remained fractionated after PVI (31% of the collected points); (ii) fractionated that converted to normal (39%); (iii) normal prior to PVI that became fractionated (9%) and; (iv) normal that remained normal (21%). Individually, the attributes failed to distinguish these LA regions, but multivariate statistical models were effective in their discrimination (P < 0.0001).Conclusion: Our results have unveiled that there are LA regions resistant to PVI, while others are affected by it. Although, traditional methods were unable to identify these different regions, the proposed multivariate statistical model discriminated LA regions resistant to PVI from those affected by it without prior ablation information.

The temporal behavior and consistency of bipolar atrial electrograms in human persistent atrial fibrillation

The unstable temporal behavior of atrial electrical activity during persistent atrial fibrillation (persAF) might influence ablation target identification, which could explain the conflicting persAF ablation outcomes in previous studies. We sought to investigate the temporal behavior and consistency of atrial electrogram (AEG) fractionation using different segment lengths. Seven hundred ninety-seven bipolar AEGs were collected with three segment lengths (2.5, 5,and 8 s) from 18 patients undergoing persAF ablation. The AEGs with 8-s duration were divided into three 2.5-s consecutive segments. AEG fractionation classification was applied off-line to all cases following the CARTO criteria; 43% of the AEGs remained fractionated for the three consecutive AEG segments, while nearly 30% were temporally unstable. AEG classification within the consecutive segments had moderate correlation (segment 1 vs 2: Spearman’s correlation ρ = 0.74, kappa score κ = 0.62; segment 1 vs 3: ρ = 0.726, κ = 0.62; segment 2 vs 3: ρ = 0.75, κ = 0.68). AEG classifications were more similar between AEGs with 5 and 8 s (ρ = 0.96, κ = 0.87) than 2.5 versus 5 s (ρ = 0.93, κ = 0.84) and 2.5 versus 8 s (ρ = 0.90, κ = 0.78). Our results show that the CARTO criteria should be revisited and consider recording duration longer than 2.5 s for consistent ablation target identification in persAF.