Endo-epicardial Asynchrony Research Articles

Identification of Atrial Transmural Conduction Inhomogeneity Using Unipolar Electrogram Morphology.

(1) Background: Structural remodeling plays an important role in the pathophysiology of atrial fibrillation (AF). It is likely that structural remodeling occurs transmurally, giving rise to electrical endo-epicardial asynchrony (EEA). Recent studies have suggested that areas of EEA may be suitable targets for ablation therapy of AF. We hypothesized that the degree of EEA is more pronounced in areas of transmural conduction block (T-CB) than single-sided CB (SS-CB). This study examined the degree to which SS-CB and T-CB enhance EEA and which specific unipolar potential morphology parameters are predictive for SS-CB or T-CB. (2) Methods: Simultaneous endo-epicardial mapping in the human right atrium was performed in 86 patients. Potential morphology parameters included unipolar potential voltages, low-voltage areas, potential complexity (long double and fractionated potentials: LDPs and FPs), and the duration of fractionation. (3) Results: EEA was mostly affected by the presence of T-CB areas. Lower potential voltages and more LDPs and FPs were observed in T-CB areas compared to SS-CB areas. (4) Conclusion: Areas of T-CB could be most accurately predicted by combining epicardial unipolar potential morphology parameters, including voltages, fractionation, and fractionation duration (AUC = 0.91). If transmural areas of CB indeed play a pivotal role in the pathophysiology of AF, they could theoretically be used as target sites for ablation.

A novel diagnostic tool to identify atrial endo-epicardial asynchrony using signal fingerprinting

ObjectivePatients with persistent atrial fibrillation (AF) have more electrical endo-epicardial asynchrony (EEA) during sinus rhythm (SR) than patients without AF. Prior mapping studies indicated that particularly unipolar, endo- and/or epicardial electrogram (EGM) morphology may be indicators of EEA. This study aim to develop a novel method for estimating the degree of EEA by using unipolar EGM characteristics recorded from either the endo- and/or epicardium. MethodsSimultaneous endo-epicardial mapping during sinus rhythm was performed in 86 patients. EGM characteristics, including unipolar voltages, low-voltage areas (LVAs), potential types (single, short/long double and fractionated potentials: SP, SDP, LDP and FP) and fractionation duration (FD) of double potentials (DP) and FP were compared between EEA and non-EEA areas. Asynchrony Fingerprinting Scores (AFS) containing quantified EGM characteristics were constructed to estimate the degree of EEA. ResultsEndo- and epicardial sites of EEA areas are characterized by lower unipolar voltages, a higher number of LDPs and FPs and longer DP and FP durations. Patients with AF have lower potential voltages in EEA areas, along with alterations in the potential types. The EE-AFS, containing the proportion of endocardial LVAs and FD of epicardial DPs, had the highest predictive value for determining the degree of EEA (AUC: 0.913). Endo- and epi-AFS separately also showed good predictive values (AUC: 0.901 and 0.830 respectively). ConclusionsEGM characteristics can be used to identify EEA areas. AFS can be utilized as a novel diagnostic tool for accurately estimating the degree of EEA. These characteristics potentially indicate AF related arrhythmogenic substrates.

PO-01-231 IDENTIFICATION OF ATRIAL ENDO-EPICARDIAL ASYNCHRONY USING SIGNAL FINGERPRINTING

Atrial three-dimensional (3D) dissociation in conduction facilitates the development of atrial fibrillation (AF). Previous mapping studies revealed that patients with persistent AF have more endo-epicardial asynchrony (EEA) during SR than those without AF. Areas of EEA can be accurately identified by using unipolar electrograms (EGM). Alterations in endo-epicardial unipolar EGM features within EEA areas may provide novel insight into the electrical substrate of AF. To develop a novel method for estimating the degree of EEA by using unipolar EGM characteristics recorded from either the endo- and/or epicardium. During SR, intra-operative simultaneous endo-epicardial mapping (256 electrodes, 2 mm interelectrode distance) of the right atrium was performed in 86 patients. EEA was defined as an endo-epicardial dissociation exceeding 15 ms. EGM features, including voltages, low voltage areas (LVAs, <1.0 mV), potential types (single, short/long double and fractionated potentials) and fractionation duration (FD) were analyzed and correlated to EEA areas. The Asynchrony Fingerprinting Score (AFS) was developed based on uni- and multivariable logistic regression analyses. Three AFSs (Epi-AFS, Endo-AFS and EE-AFS) were established and assessed. EEA areas were characterized by a decrease in potential voltages, an increase in the number of long double potentials (LDPs) and fractionated potentials (FPs) and prolongation of double potentials (DPs) and FPs compared to non-EEA areas. Epi-AFS contained epicardial median voltage and the proportion of LDP, whereas the Endo-AFS contained the endocardial proportion of LVAs and single potentials (SPs). The EE-AFS, containing the proportion of endocardial LVAs, and the FD of epicardial DPs, showed the highest predictive value (AUC: 0.913) in determining the degree of EEA, although both Epi- and Endo-AFS also showed good predictive value with AUCs of 0.830 and 0.901 respectively. EEA is characterized by increased amounts of LVAs, LDPs and FPs, as well as an increase in the duration of both DPs and FPs. Epi-, Endo- and EE-AFS all showed good accuracy in identifying EEA areas. Therefore, AFS, as a novel approach utilizing integrated data from endo- or/and epicardium, may enable precise identification of EEA degree, including potentially arrhythmogenic substrates.

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.

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.

Novel insights in pathophysiology of postoperative atrial fibrillation

ObjectivesAtrial extrasystoles are usually benign; however, they can also trigger atrial fibrillation. It is most likely that if atrial extrasystoles provoke a larger amount of conduction disorders and a greater degree of endo-epicardial asynchrony, the risk of postoperative atrial fibrillation increases. To test this hypothesis, we investigated the effect of programmed atrial extrasystoles on endo-epicardial conduction and postoperative atrial fibrillation. MethodsTwelve patients (58% male, age 68 ± 7 years) underwent simultaneous endo-epicardial mapping (256 electrodes) of the right atrium during sinus rhythm and programmed atrial extrasystoles provoked from the right atrial free wall. Areas of conduction block were defined as conduction delays of ≥12 milliseconds and endo-epicardial asynchrony as activation time differences of exact opposite electrodes of ≥15 milliseconds. ResultsEndo-epicardial mapping data of all programmed atrial extrasystoles were analyzed and compared with sinus rhythm (median preceding cycle length = 531 milliseconds [345-787] and median sinus rhythm cycle length = 843 milliseconds [701-992]). All programmed atrial extrasystoles were aberrant (severe, moderate, and mildly aberrant, respectively, n = 6, 3, and 3) and had a mean prematurity index of 50.1 ± 11.9%. The amount of endo-epicardial asynchrony (1% [1-2] vs 6.7 [2.7-16.9], P = .006) and conduction block (1.4% [0.6-2.6] vs 8.5% [4.2-10.4], P = .005) both increased during programmed atrial extrasystoles. Interestingly, conduction block during programmed atrial extrasystoles was more severe in patients (n = 4, 33.3%) who developed postoperative atrial fibrillation (5.1% [2.9-8.8] vs 11.3% [10.1-12.1], P = .004). ConclusionsAtrial conduction disorders and endo-epicardial asynchrony, which play an important role in arrhythmogenesis, are enhanced during programmed atrial extrasystoles compared with sinus rhythm. The findings of this pilot study provide a possible explanation for enhanced vulnerability for postoperative atrial extrasystoles to induce postoperative atrial fibrillation in patients after cardiac surgery.

Endo-Epicardial Mapping of InVivo Human Sinoatrial Node Activity.

The aim of the current study was to examine electrophysiological characteristics of sinoatrial node (SAN) activity from an endo-epicardial perspective. Electrophysiological properties of the invivo human SAN and its exit pathways remain poorly understood. Twenty patients (75% male; median age 66 years [59 to 73 years]) with structural heart disease underwent simultaneous endo-epicardial mapping (256 unipolar electrodes, interelectrode distance 2mm). Conduction times, endo-epicardial delays (EEDs), and R/S ratio were examined in the surrounding 10mm of SAN activation. Areas of conduction block were defined as conduction delays≥12ms and endo-epicardial asynchrony as EED≥15 m. Three distinct activation patterns were observed in a total of 28 SAN-focal activation patterns (SAN-FAPs) (4 patients exhibited >1 different exit site), including SAN activation patterns with: 1) solely an endocardial exit site (n=10 [36%]); 2) solely an epicardial exit site (n=13 [46%]); and 3) simultaneously activated endo-epicardial exit sites (n=5 [18%]). Median (interquartile range) EED at the origin of the SAN-FAP was 10ms (6 to 14 ms) and the prevalence of endo-epicardial asynchrony in the surroundings of the SAN-FAP was 5% (2% to 18%). Electrograms at the origin of the SAN-FAPs exhibited significantly larger R-peaks in the mid right atrium (RA) compared with the superior RA (mid R/S ratio 0.15 [0.067 to 0.34] vs. superior R/S ratio 0.045 [0.026 to 0.062]; p=0.004). Conduction velocity within a distance of 10mm from the SAN-FAP was 125cm/s (80 to 250 cm/s). All 6 SAN-FAPs at the mid RA were observed in patients with a history of atrial fibrillation. Variations in activation patterns of the SAN observed in this study highlight the complex 3-dimensional SAN geometry and indicate the presence of interindividual differences in SAN exit pathways. Solely in patients with a history of atrial fibrillation, SAN activity occurred more caudally, which indicates changes in preferential SAN exitpathways.

Simultaneous endo-epicardial mapping of programmed atrial extrasystoles in patients undergoing cardiac surgery

Abstract Introduction Atrial extrasystoles (AES) are usually innocent, however they can also trigger (post-operative) atrial fibrillation (AF). It is unknown what the arrhythmogenic effect of AES is on 3-dimensional atrial conduction. Purpose Therefore, the aim of this study was to examine the effect of programmed AES (PAES) provoked in the right atrium (RA) on both endo- and epicardial conduction. Methods Simultaneous endo-epicardial mapping of the RA was performed during PAES provoked from the RA free wall in patients undergoing cardiac surgery (256 electrodes). Areas of conduction block (CB) were defined as conduction delays of ≥12ms and endo-epicardial asynchrony (EEA) as activation time differences of exact opposite electrodes of ≥15ms. Results Simultaneous endo-epicardial mapping of the RA during 15 PAES were analyzed and compared with sinus rhythm (SR) (n=12, 58% male, age 68±7 years). Eleven PAES were premature (&amp;gt;25% shortening cycle length (CL)), median preceding CL was 554.5ms [377.9–720.4] and median SR CL was 871ms [700.9–1021]. Amount of EEA (7.3% [2.6–17.8] vs 1% [1–2], p=0.002) and CB (9% [4.8–11.8] vs 1.4% [0.5–2.7, p=0.001) both increased during PAES compared to SR. Diabetes was the only cardiovascular risk factor associated with a higher incidence and degree of EEA and CB. Interestingly, CB during PAES was more severe in 4 patients (33.3%) who developed post-operative AF (11.9% [10.4–12.8] vs 5.4% [3.3–8.5], p&amp;lt;0.001). Conclusion Asynchronous activation of the atrial wall and conduction disorders, which play an important role in arrhythmogenesis, are enhanced during PAES compared to SR. Enhanced electropathology together with triggers provoked by heart surgery may initiate post-operative AF. Funding Acknowledgement Type of funding source: None

Simultaneous endo-epicardial mapping of the human sinus node in patients undergoing cardiac surgery

Abstract Introduction Conduction disorders in the right atrium (RA) are predominantly observed in the superior part. Presence of the sinoatrial node (SAN) in this region could be contributing to increased heterogeneity in activation patterns. However, mapping studies focusing on SAN activation are scarce. Purpose The aim of the present study was to analyze activation patterns of the human SAN during sinus rhythm. Methods A dataset containing simultaneous endo-epicardial mapping data (256 electrodes, inter-electrode spacing: 2mm) of RA was screened for focal activation patterns (FAPs) potentially arising from SAN activation (SN-FAP). Conduction time, endo-epicardial delay and electrogram morphology (R/S-ratio) were described in the surrounding 1cm of SN-FAPs. Areas of conduction block (CB) were defined as conduction delays of ≥12ms and endo-epicardial asynchrony (EEA) as activation time differences of exact opposite electrodes of ≥15ms. Results In 20 patients (75% male, 66±7 years) a total of 28 SN-FAPs with unique activation patterns were observed only in superior RA (n=22) and mid RA (n=6). Conduction velocity of SN-FAPs was 1.3m/s [0.8–2.5] and percentage of EEA was 5% [2–18]. Conduction velocity was lower when lines of CB were present within 6mm of the SN-FAPs (p=0.040). Significantly larger R-peaks were observed in mid RA compared to superior RA. (mid R/S-ratio:0.15 [0.067–0.34] vs. superior R/S-ratio:0.045 [0.026–0.062], p=0.004). Conclusions Conduction velocities around the SAN area are comparable to the remainder of the atria. SN-FAPs occurred in both superior and mid RA, suggesting presence of multiple exit sites of the SAN. Furthermore, inter-individual differences in rS-morphology indicate that SAN activation may originate from multiple layers within the atrial wall. Funding Acknowledgement Type of funding source: None

P984Proof of endo-epicardial asynchrony of the left atrial wall in humans

Abstract Funding Acknowledgements Prof. Dr. NMS de Groot is supported by funding grants from CVON-AFFIP (914728), NWO-Vidi (91717339), Biosense Webster USA (ICD 783454) and Medical Del Introduction Treatment of atrial fibrillation (AF) is still suboptimal as mechanisms underlying AF initiation and persistence are incompletely understood. Endo-Epicardial asynchrony (EEA) plays an important role in AF persistence and has so far only been demonstrated in the right atrium (RA). Purpose To investigate whether EEA also exists in the thin walled left atrium (LA) and to measure the maximal degree of EEA between the endo- and epicardial layers during sinus rhythm (SR). Methods Simultaneous endo-epicardial mapping of the LA was performed during SR in 3 male patients (73 ± 1.5 years) with history of paroxysmal AF undergoing cardiac surgery including rhythm surgery and LA appendage amputation. Simultaneous endo-epicardial mapping was performed with a mapping clamp containing two electrode arrays of 8x16 electrodes (diameters: 0.4mm, interelectrode distance: 2mm) positioned exactly opposite to each other. The mapping clamp was introduced through the LA appendage with its tip towards the superior pulmonary vein. Local endo-epicardial activation time differences were determined by selecting the median time delay within the exact opposite electrode and its 8 surrounding electrodes. The asynchrony map consisted of the maximum of 2 medians from direct opposite electrodes. EEA was defined as time differences ≥15ms. Conduction delay (CD) and conduction block (CB) were defined as differences in local activation times between neighboring electrodes of respectively ≥7 and ≥12ms. Results A total of 35 SR beats were analyzed. Mean total activation time of the whole endo-epicardial LA tissue was 42.4 ± 9.5ms and did not differ between both layers (epicardium: 31.2 ± 9.9ms; endocardium: 37.8 ± 10.3ms; P= 0.62). CD and CB were observed in respectively 3.2% and 6.3% at the epicardium and 3.3% and 3.0% at the endocardium. The lowest amount of CD (5.2%) and CB (0.3%) was observed in the patient who had his first AF episode only 11 days prior to surgery. Also, no EEA was present in this patient. In two patients with paroxysmal AF &amp;gt;6 months, the prevalence of EEA was respectively 2.7% and 41.4% and the degree of EEA ranged from 15 to 44ms. Interestingly, the patient with the highest degree of EEA was diagnosed with paroxysmal AF for almost 5 years (Figure 1). Conclusion Our data provides evidence for the existence of EEA in the human left atrium which appears to be already present during SR. Knowledge of EEA and the ability to stage AF based on the degree of EEA is essential for individualized and staged future therapy for AF. Abstract Figure 1. The maximal degree of endo-epi

P380Simultaneous endo-epicardial mapping of the human right atrium: unravelling 3-dimensional excitation

Abstract Funding Acknowledgements Prof. Dr. NMS de Groot is supported by funding grants from CVON-AFFIP (914728), NWO-Vidi (91717339), Biosense Webster USA (ICD 783454) and Medical Del Abstract Introduction &amp; Purpose Mapping studies demonstrated that endo-epicardial asynchrony (EEA) and conduction disorders, mainly longitudinal dissociation, play an important role in the pathophysiology of atrial fibrillation (AF). The aim of our study was therefore to investigate the correlation between features of conduction disorders assessed in the endo- and epicardial plane and the degree of EEA. Methods In 80 patients (63 male (79%), age 66 ± 9 years, 31 history of AF (39%)) undergoing cardiac surgery, simultaneous endo-epicardial mapping (256 electrodes, interelectrode distance:2mm) of the inferior, middle and superior right atrium (RA) was performed during SR. Areas of conduction block (CB) were defined as conduction delays of ≥12ms, EEA as activation time differences of opposite electrodes of ≥15ms and transmural CB as CB at similar endo-epicardial sites. Results Amount of CB was highest at the endocardium (endo median:1.9% [0-21.6] vs. epi median:1.1% [0-19.2], all locations p &amp;lt; 0.025) and was more pronounced at the superior RA. Amount of conduction block at both the endo-epicardium combined was higher at the superior RA in patients with hypertension (p = 0.046). Likewise, prevalence of transmural CB and EEA,-up to 84ms-, significantly increased from inferior to superior RA (all p &amp;lt; 0.001). Transmural CB at the inferior RA appeared to be associated with a higher incidence of post-operative AF (p = 0.03). Degree of EEA was also highest at superior RA (superior: 17.5ms [16-21.75] vs mid: 17ms [0-20] and inferior: 0ms [0-17], p &amp;lt; 0.001). Prevalence of CB was correlated with prevalence EEA (r= 0.74-0.87; all locations p &amp;lt; 0.001). In patients with hypertension (p = 0.009), diabetes (p = 0.015) and hypercholesterolemia (p = 0.015), EEA degree was higher at inferior RA. Significantly more CB (p = 0.007) and EEA (p = 0.037) were observed in patients with a history of persistent AF compared to patients without AF history. Conclusions This study provides important insights into the complex 3-dimensional endo-epicardial excitation and arrhythmogenesis. Knowledge of 3-dimensional excitation during SR is essential to understand the substrate underlying AF in order to improve (ablative) AF therapy.

Atrial Ectopy Increases Asynchronous Activation of the Endo- and Epicardium at the Right Atrium.

The predisposition of atrial extrasystoles (AES) to trigger cardiac tachyarrhythmia may arise from intramural conduction disorders causing endo-epicardial asynchrony (EEA). This study aimed to determine whether spontaneous AES disturb endo-epicardial conduction. Simultaneous endo-epicardial mapping of the right atrium was performed in patients during cardiac surgery with two 128-electrode arrays. Sixty spontaneous AES were observed in 23 patients and were analyzed for incidence of conduction delay, conduction block and amount of EEA compared to the previous sinus rhythm beat. Both conduction delay and block occurred more often in AES compared to sinus rhythm. The difference in lines of conduction block between the epicardium and endocardium increased in AES causing a greater imbalance of conduction disorders between the layers. The incidence of EEA with differences ≥10 ms increased significantly in AES. AES caused delays between the epicardium and endocardium up to 130 ms and EEA to increase for up to half (47%) of the mapping area. Conduction disturbances between the epicardial and endocardial layer giving rise to EEA increase during AES. Asynchronous activation of the atrial layers increases during AES which may be a mechanism for triggering cardiac tachyarrhythmia under the right conditions but EEA cannot be recognized by current mapping tools.

Pathophysiology of atrial fibrillation: Focal patterns of activation.

For decades, electrical activity recorded has been investigated to unravel pathophysiology of cardiac arrhythmias, such as atrial fibrillation (AF). Particularly high-resolution mapping studies have significantly contributed to novel insights into AF mechanisms. From these mapping studies, it appeared that persistence of AF is associated with a high incidence of focal patterns of activation. Features of these focal activation patterns indicated that they could be attributed to transmural propagation of fibrillation waves. However, "focal fibrillation waves" can only appear when there is electrical asynchrony between the endocardial and epicardial layer. By performing simultaneous high-resolution mapping of the endo- and epicardial wall of the right atrium in humans during AF, the existence of electrical asynchrony (endo-epicardial asynchrony [EEA]) between the endo- and epicardial layer was indeed confirmed. During sinus rhythm, focal patterns of activation are most frequently observed at the right atrium and a considerable degree of EEA-as large as 50ms-may occur. Furthermore, prematurely aberrant atrial extrasystoles emerging as focal waves caused the highest degree of conduction disorders, particularly in patients with left atrial dilatation and diabetes mellitus. These observations emphasize the contribution of atrial anatomy to EEA and the role of focal patterns of activation in development AF.

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.

Epicardial Breakthrough Waves During Sinus Rhythm: Depiction of the Arrhythmogenic Substrate?

Epicardial breakthrough waves (EBW) during atrial fibrillation are important elements of the arrhythmogenic substrate and result from endo-epicardial asynchrony, which also occurs to some degree during sinus rhythm (SR). We examined the incidence and characteristics of EBW during SR and its possible value in the detection of the arrhythmogenic substrate associated with atrial fibrillation. Intraoperative epicardial mapping (interelectrode distances 2 mm) of the right atrium, Bachmann's bundle, the left atrioventricular groove, and the pulmonary vein area was performed during SR in 381 patients (289 male, 67±10 years) with ischemic or valvular heart disease. EBW were referred to as sinus node breakthrough waves if they were the earliest right atrial activated site. A total of 218 EBW and 57 sinus node breakthrough waves were observed in 168 patients (44%). EBW mostly occurred at right atrium (N=105, 48%) and left atrioventricular groove (N=67, 31%), followed by Bachmann's bundle (N=27, 12%) and pulmonary vein area (N=19, 9%; P<0.001). EBW occurred most often in ischemic heart disease patients (N=114, 49%) compared with (ischemic and) valvular heart disease patients (N=26, 17%; P<0.001). EBW electrograms most often consisted of double and fractionated potentials (N=137, 63%). In case of single potentials, an R wave was observed in 88% (N=71) of EBW, as opposed to 21% of sinus node breakthrough waves (N=5; P<0.001). Fractionated EBW potentials were more often observed at the right atrium and Bachmann's bundle (P<0.001). During SR, EBW are present in over a third of patients, particularly in thicker parts of the atrial wall. Features of SR EBW indicate that muscular connections between endo- and epicardium underlie EBW and that a slight degree of endo-epicardial asynchrony required for EBW to occur is already present in some areas during SR. Hence, an anatomic substrate is present, which may enhance the occurrence of EBW during atrial fibrillation, thereby promoting atrial fibrillation persistence.

Direct Proof of Endo-Epicardial Asynchrony of the Atrial Wall During Atrial Fibrillation in Humans.

The presence of focal fibrillation waves during atrial fibrillation (AF) can, besides ectopic activity, also be explained by asynchronous activation of the atrial endo- and epicardial layer and transmurally propagating fibrillation waves. To provide direct proof of endo-epicardial asynchrony, we performed simultaneous high-resolution mapping of the right atrial endo- and epicardial wall during AF in humans. Intraoperative mapping of the endo- and epicardial right atrial wall was performed during (induced) AF in 10 patients with AF (paroxysmal: n=3; persistent: n=4; and longstanding persistent: n=3) and 4 patients without a history of AF. A clamp made of 2 rectangular 8×16 electrode arrays (interelectrode distance 2 mm) was inserted into the incision in the right atrial appendage. Recordings of 10 seconds of AF were analyzed to determine the incidence of asynchronous endo-epicardial activation times (≥15 ms) of opposite electrodes. Asynchronous endo-epicardial activation ranged between 0.9 and 55.9% without preference for either side. Focal waves appeared equally frequent at endocardium and epicardium (11% versus 13%; ITALIC! P=0.18). Using strict criteria for breakthrough (presence of an opposite wave within 4 mm and ≤14 ms before the origin of the focal wave), the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. We provided the first evidence for asynchronous activation of the endo-epicardial wall during AF in humans. Endo-epicardial asynchrony may play a major role in the pathophysiology of AF and may offer an explanation why in some patients therapy fails.