Epicardial Mapping Studies Research Articles

Atrial contractile and electrical remodeling is associated with more complex conduction patterns in patients without history of atrial fibrillation: a high-density epicardial mapping study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by the Netherlands Heart Foundation (CVON2014-09, RACE V Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF), the European Union (ITN Network Personalized Therapies for Atrial Fibrillation: a translational network: PersonalizeAF, grant 860974, CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly, No. 633196). Background Early atrial remodeling refers to a concept where atrial structural, functional, and electrophysiological changes may be present without clinical manifestation of atrial arrhythmias. (1) However, it is currently unknown how electrophysiological and functional atrial properties are related, especially in the early stages of atrial remodeling. Purpose To investigate the relationship between electrophysiological properties of the atria, determined by intraoperative high-density epicardial mapping after AF-induction, and echocardiographic and electrocardiographic parameters in patients without a history of AF undergoing cardiac surgery. Methods All patients underwent functional and electrophysiological analysis of both atria using preoperative transthoracic echocardiography, electrocardiography, and intraoperative biatrial high-density epicardial mapping. Postoperatively, all patients were continuously monitored for occurrence of new-onset postoperative AF (POAF). In addition to univariable and multivariable analysis, cluster analysis was performed to identify distinct clusters of subjects for epicardial mapping parameters. Results The study population consisted of 38 patients undergoing coronary artery bypass grafting, isolated aortic valve replacement, or the combination of both. All patients completed 1-year continuous rhythm monitoring and 19 patients (50%) developed POAF. There was a greater number of waves/cycle (4.57±1.55 vs. 3.98±1.63, p=0.04) and breakthrough (BT) waves/cycle (1.16±0.58 vs. 0.88±0.60, p=0.01) in the RA compared to the LA (Figure 1). Also, there was a lower conduction velocity (CV) in the RA than in the LA (0.71±0.10m/s vs 1.19±0.36m/s, p<0.01) (Figure 1). Average waves/cycle were significantly correlated with reduced P-wave duration and P-wave amplitude (Spearman’s rho=-0.32, p=0.04, and Spearman’s rho=-0.32, p=0.04, respectively). Also, there was significant negative correlation between LA booster function and LA waves/cycle (Spearman’s rho=-0.55, p<0.01). Survival analysis revealed that older age, lower P-wave amplitude, reduced LA booster function, and increased RA waves/cycle were associated with increased occurrence of POAF (Figure 2). Cluster analysis was performed for RA and LA epicardial mapping parameters, which identified 2 distinct clusters: cluster 1 consisted of patients with more complex atrial electrical conduction patterns, and cluster 2 less complex atrial electrical conduction patterns. Multivariable analysis showed that reduced LA booster function was independently associated with a cluster representing more complex atrial electrical conduction patterns in the LA (OR=1.13, 95% CI: 1.02-1.25, p=0.02). Conclusion In patients without a history of AF, reduced LA contractile function and lower P-wave amplitude are associated with more complex electrical conduction patterns in acutely induced AF, potentially representing an early step in the atrial remodeling process.

Intrapericardial cardiosphere-derived cells hinder epicardial dense scar expansion and promote electrical homogeneity in a porcine post-infarction model.

The arrhythmic substrate of ventricular tachycardias in many structural heart diseases is located in the epicardium, often resulting in poor outcomes with currently available therapies. Cardiosphere-derived cells (CDCs) have been shown to modify myocardial scarring. A total of 19 Large White pigs were infarcted by occlusion of the mid-left anterior descending coronary artery for 150min. Baseline cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement sequences was obtained 4 weeks post-infarction and pigs were randomized to a treatment group (intrapericardial administration of 300,000 allogeneic CDCs/kg), (n = 10) and to a control group (n = 9). A second CMR and high-density endocardial electroanatomical mapping were performed at 16weeks post-infarction. After the electrophysiological study, pigs were sacrificed and epicardial optical mapping and histological studies of the heterogeneous tissue of the endocardial and epicardial scars were performed. In comparison with control conditions, intrapericardial CDCs reduced the growth of epicardial dense scar and epicardial electrical heterogeneity. The relative differences in conduction velocity and action potential duration between healthy myocardium and heterogeneous tissue were significantly smaller in the CDC-treated group than in the control group. The lower electrical heterogeneity coincides with heterogeneous tissue with less fibrosis, better cardiomyocyte viability, and a greater quantity and better polarity of connexin 43. At the endocardial level, no differences were detected between groups. Intrapericardial CDCs produce anatomical and functional changes in the epicardial arrhythmic substrate, which could have an anti-arrhythmic effect.

Does conduction heterogeneity determine the supervulnerable period after atrial fibrillation?

Atrial fibrillation (AF) resumes within 90 s in 27% of patients after sinus rhythm (SR) restoration. The aim of this study is to compare conduction heterogeneity during the supervulnerable period immediately after electrical cardioversion (ECV) with long-term SR in patients with AF. Epicardial mapping of both atria was performed during SR and premature atrial extrasystoles in patients in the ECV (N = 17, age: 73 ± 7 years) and control group (N = 17, age: 71 ± 6 years). Inter-electrode conduction times were used to identify areas of conduction delay (CD) (conduction times 7–11 ms) and conduction block (CB) (conduction times ≥ 12 ms). For all atrial regions, prevalences and length of longest CB and continuous CDCB lines, magnitude of conduction disorders, conduction velocity, biatrial activation time, and voltages did not differ between the ECV and control group during both SR and premature atrial extrasystoles (p ≥ 0.05). Hence, our data suggest that there may be no difference in biatrial conduction characteristics between the supervulnerable period after ECV and long-term SR in AF patients.Graphical abstractThe supervulnerable period after AF termination is not determined by conduction heterogeneity during SR and PACs. It is unknown to what extent intra-atrial conduction is impaired during the supervulnerable period immediately after ECV and whether different right and left atrial regions are equally affected. This high-resolution epicardial mapping study (upper left panel) of both atria shows that during SR the prevalences and length of longest CB and cCDCB lines (upper middle panel), magnitude of conduction disorders, CV and TAT (lower left panel), and voltages did not differ between the ECV and control group. Likewise, these parameters were comparable during PACs between the ECV and control group (lower left panel). †Non-normally distributed. cm/s = centimeters per second; mm = millimeter; ms = millisecond; AF = atrial fibrillation; AT = activation time; BB = Bachmann’s bundle; cCDCB = continuous lines of conduction delay and block; CB = conduction block; CD = conduction delay; CT = conduction time; CV = conduction velocity; ECV = electrical cardioversion; LA = left atrium; LAT = local activation times; PAC = premature atrial complexes; PVA = pulmonary vein area; RA = right atrium; SR = sinus rhythm; TAT = total activation time.

Low-level vagus nerve stimulation during cardiac surgery: smart neuromodulation

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): CVON-AFFIP Dutch Heart Foundation Objective The goal of this study is to unravel the anti-arrhythmogenic effects of low-level vagus nerve stimulation (LL-VNS) by performing high-resolution and high-density epicardial mapping studies before and after transcutaneous LL-VNS in patients undergoing primary cardiac surgery. Background Vagus nerve stimulation has pro-arrhythmogenic and anti-arrhythmogenic properties. LL-VNS has been proven to reduce AF incidence and burden, but the anti-arrhythmogenic effect of LL-VNS remains largely unexplored thereby hampering clinical implementation and optimal patient selection. Methods 10 patients (90% male, age 75±6 years) undergoing coronary artery bypass surgery (CABG) were included in this study. Epicardial sinus rhythm mapping of the right atrium and Bachmann’s bundle (BB) was performed prior, after acute- and chronic transcutaneous LL-VNS. Results LL-VNS did not result in any significant changes in potential fractionation, conduction block, conduction velocity or voltage. Potential duration prolonged from 37.5 [31.0-56.0] ms to 48 [36.0-50.0] ms during acute (p=0.002) and 52.5 [45.8-61.0] ms during chronic LL-VNS (p=0.007). Conclusions This is the first epicardial mapping study in humans investigating the effect of LL-VNS on atrial conduction. Compared to no LL-VNS, acute and chronic LL-VNS prolonged potential duration significantly.

Melatonin treatment improves ventricular conduction via upregulation of Nav1.5 channel proteins and sodium current in the normal rat heart

Melatonin treatment was reported to reduce the risk of cardiac arrhythmias, and crucial for this antiarrhythmic action was the effect of melatonin on activation spread. The aim of the present study was evaluation of the mechanisms of this activation enhancement.Experiments were performed in a total of 123 control and melatonin-treated (10 mg/kg, daily, for 7 days) male Wistar rats. In epicardial mapping studies (64 leads, interlead distance 0.5 mm) in the anesthetized animals, activation times (ATs) were determined in each lead as dV/dt minimum during QRS complex under sinus rhythm. Epicardial pacing was performed to measure conduction velocity (CV) across the mapped area. Average left ventricular ATs were shorter in the treated animals as compared to the controls, whereas the minimal epicardial ATs indicating the duration of activation propagation via the ventricular conduction system did not differ between the groups. CV was higher in the treated groups indicating that melatonin affected conduction via contractile myocardium The area of Cx43-derived fluorescence, as well as the expression of Cx43 protein, was similar in ventricles in the control and melatonin-treated groups. Expression of Gja1 gene transcripts encoding Cx43, was increased in the last group. An uncoupling agent octanol modified myocardial conduction properties (time of activation, action potential upstroke velocity, passive electrotonic phase duration) similarly in both groups. On the other hand, the expression of both Scn5a gene transcripts encoding Nav1.5 proteins, as well as peak density of transmembrane sodium current were increased in the ventricular myocytes from the melatonin-treated animals. Thus, a week-long melatonin treatment caused the increase of conduction velocity via enhancement of sodium channel proteins expression and increase of sodium current in the ventricular myocytes.

Apelin Inhibits Angiotensin II-Induced Atrial Fibrosis and Atrial Fibrillation via TGF-β1/Smad2/α-SMA Pathway.

BackgroundAngiotensin II (Ang II) could promote the development of atrial fibrosis in atrial fibrillation (AF). Apelin can inhibit the occurrence of myocardial fibrosis. However, the effect of apelin on Ang II-induced atrial fibrosis and subsequent AF still remains unknown.ObjectiveIn the present study, we examined the effect of apelin on the suppression of atrial fibrosis and subsequent AF, and investigated its underlying mechanisms.MethodsSprague-Dawley rats were treated for 2 weeks with Ang II (1080 μg/kg/24 h) and apelin-13 (140 μg/kg/24 h) using implantable mini-pumps. The incidence of AF induced by atrial pacing was determined. Atrial electrophysiological mapping was recorded by a 32-electrode microelectrode array. Blood was collected to measure the levels of Ang II and apelin. Atrial tissue samples were preserved to assess the pathohistological changes, DDR2 and α-SMA co-staining were performed, and the protein expression of Smad2 phosphorylation was evaluated.ResultsApelin significantly inhibited Ang II-induced atrial fibrosis (HE:1.45 ± 0.11 vs 6.12 ± 0.16, P < 0.001; Masson:1.49 ± 0.25 vs 8.15 ± 0.23, P < 0.001; Picrosirius Red:1.98 ± 0.64 vs 9.59 ± 0.56, P < 0.001, respectively) and decreased the vulnerability of AF (inducibility of AF: z = −4.40, P < 0.001; total AF duration: z = −4.349, P < 0.001). Left atrial epicardial mapping studies demonstrated preservation of atrial conduction homogeneity by apelin. The protective effects of apelin from fibrotic remodeling were mediated by suppression of Smad2-dependent fibrosis.ConclusionApelin potently inhibited Ang II-induced atrial fibrosis and subsequent vulnerability to AF induction via suppression TGF-β/Smad2/α-SMA pathway. Our results indicated that apelin might be an effective up-stream therapy for atrial fibrosis and AF.

His bundle pacing shows similar ventricular electrical activation as sinus: selective and nonselective His pacing indistinguishable

His bundle pacing utilizes the His-Purkinje system to produce more physiological activation compared with traditional pacing therapies, but differences in electrical activation between pacing techniques are not yet quantified in terms of activation pattern. Furthermore, clinicians distinguish between selective and nonselective His pacing, but measurable differences in electrical activation remain to be seen. Hearts isolated from seven dogs were perfused using the Langendorff method. Electrograms were recorded using two 64-electrode basket catheters in the ventricles and a 128-electrode sock situated around the ventricles during sinus rhythm (right atrial pacing), right ventricular (RV) pacing, biventricular cardiac resynchronization therapy (biV-CRT), selective His pacing (selective capture of the His bundle), and nonselective His pacing (capture of nearby myocardium and His bundle). Activation maps were generated from these electrograms. Total activation time (TAT) was measured from the activation maps, and QRS duration was measured from a one-lead pseudo-ECG. Results showed that TAT, QRS duration, and activation sequence were most similar between sinus, selective, and nonselective His pacing. Bland-Altman analyses showed highest levels of similarity between all combinations of sinus, selective, and nonselective His pacing. RV and biV-CRT activation patterns were distinct from sinus and had significantly longer TAT and QRS duration. Cumulative activation graphs were most similar between sinus, selective, and nonselective His pacing. In conclusion, selective pacing and nonselective His bundle pacing are more similar to sinus compared with RV and biV-CRT pacing. Furthermore, selective pacing and nonselective His bundle pacing are not significantly different electrically.NEW & NOTEWORTHY Our high-density epicardial and endocardial electrical mapping study demonstrated that selective pacing and nonselective His bundle pacing are more electrically similar to sinus rhythm compared with right ventricular and biventricular cardiac resynchronization therapy pacing. Furthermore, small differences between selective and nonselective His bundle pacing, specifically a wider QRS in nonselective His pacing, do not translate into significant differences in the global activation pattern.

P1006Conduction disorders in patients with congenital heart disease and right atrial volume overload: an intraoperative epicardial mapping study

Abstract Background Various atrial regions may contribute to the arrhythmogenic substrate for atrial tachyarrhythmias, including atrial fibrillation (AF), in patients with right atrial (RA) volume overload in congenital heart disease (CHD). It is widely recognized that structural and electrical remodelling of the RA occurs, but a previous endovascular mapping study showed that the left atrium (LA) was also affected in patients with atrial septal defect (ASD). The role of Bachmann's bundle (BB) and posterior left atrium (PLA) is yet unknown. Purpose To quantify and compare prevalence and severity of conduction disorders during sinus rhythm between atrial regions in patients with CHD and RA volume overload, using intraoperative high-resolution epicardial mapping. Methods Thirty-one patients (female: n=18, age: 48.5±13.8 years, history of AF: n=5) undergoing cardiac surgery for secundum ASD (n=18), sinus venosus defect (n=11) or isolated partial abnormal pulmonary venous return (n=2) were included. Intra-operative epicardial mapping (N=128/192 electrodes, interelectrode distance: 2mm) of the RA, BB, LA and PLA was performed during sinus rhythm. Conduction delay (CD) and block (CB) were quantified per region as proportion (%), length of lines (mm) and maximum conduction time (Δ local activation time between two adjacent electrodes). Results Proportion of CD on BB was 3.9% (2.3–4.9), RA 3.1% (1.9–3.8), PLA 2.4% (1.2–3.6) and LA 2.3% (1–3) and was higher on BB compared to PLA (p=0.002) and LA (p&lt;0.001) but not RA (p=0.063). Proportion of CB on BB was 2.1% (1.2–5.4), RA 2.2% (1.1–3.4), PLA 0.8% (0.1–2.4) and LA 0.8% (0.3–1.6) and was smaller on LA compared to BB (p=0.001) and RA (p=0.004). There were no significant differences in length of CD/CB lines between regions, except that length of the longest CB line per patient was longer in the RA compared to LA (p=0.008). Maximum conduction time was highest in the RA (median 40ms) as opposed to BB (31ms), LA (21ms) and PLA (18ms; all p&lt;0.0083 with Bonferroni correction), suggesting conduction disorders were more severe in the RA. For sub analysis, the RA surface was divided into 1) the crista terminalis region and 2) the lateral RA wall. In the crista terminalis region, proportions of CD and CB were higher, CD/CB lines were longer and maximum conduction times were higher (all p&lt;0.05). Differences between patients with and without AF were solely observed on BB: patients with AF had a higher proportion and longer lines of CB (p&lt;0.05), though outcomes should be interpreted with caution due to the small number of patients with AF. Conclusions In adult patients with CHD and RA volume overload, both RA and BB were affected by conduction disorders. More specifically, conduction disorders in the RA were mainly concentrated in the crista terminalis region. These findings suggest that not only the RA but also BB may be involved in the arrhythmogenic substrate for atrial tachyarrhythmias in these patients. Acknowledgement/Funding Dutch Heart Foundation [no 2012T0046]; LSH-Impulse [no 40-43100-98-008]; CVON [no 914728] and VIDI [no 91717339] to N.M.S. de Groot.

1004Impact of ischemic and valvular heart disease on atrial excitation: a high-resolution epicardial mapping study

1004Impact of ischemic and valvular heart disease on atrial excitation: a high-resolution epicardial mapping study

P852Impact of ischemic and valvular heart disease on atrial excitation: a high-resolution epicardial mapping study

P852Impact of ischemic and valvular heart disease on atrial excitation: a high-resolution epicardial mapping study

The effect of electrode density on the interpretation of atrial activation patterns in epicardial mapping of human persistent atrial fibrillation

Mechanisms sustaining human persistent atrial fibrillation (AF) remain debated, with significant differences between high-density epicardial and global endocardial mapping studies. A key difference is the density of recording electrodes. We aimed to determine the differences in the prevalence of different atrial activation patterns, and specifically in the prevalence of rotational activations, with varying densities of bipolar electrodes. Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded using a triangular plaque (6.75 cm(2) area; 117 bipoles; 2.5-mm inter-bipole spacing) applied to the left atrial posterior wall or right atrial free wall. Dynamic wavefront mapping based on the timing of atrial electrograms was applied to 2 discrete 10-second AF segments. The spacing between bipolar electrode locations was increased from 2.5 × 3.5 mm in the horizontal and oblique directions to 5.0 × 3.5, 5.0 × 7.1, and 7.5 × 10.6 mm, with wavefront mapping repeated at each density. As density reduced, there was a significant change in relative proportions of the various activation patterns (F=3.69; P < .001). Simple broad wavefront activations became more prevalent (20% ± 8% to 54% ± 8%; P < .05) and complex patterns became less prevalent (48% ± 8% to 9% ± 8%; P < .05) with reducing density. The prevalence of rotational activity declined with bipole density, from median 5.0% (range 0.9%-12.1%) to 0% (range 0%-1.5%) (P = .03). The largest change occurred between inter-bipole spacings of 5.0 × 3.5 and 5.0 × 7.1 mm. Apparent activation patterns in persistent AF vary significantly with electrode density. Low density underestimates the prevalence of complex and rotational patterns. The largest difference occurs between an inter-bipole spacing of 5.0 × 3.5 and a spacing of 5.0 × 7.1 mm. This may have important implications for mapping technology design.

Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation.

Atrial fibrosis, one of the most striking features in the pathology of atrial fibrillation (AF), is promoted by local and systemic inflammation. Electrophilic fatty acid nitroalkenes, endogenously generated by both metabolic and inflammatory reactions, are anti-inflammatory mediators that in synthetic form may be useful as drug candidates. Herein we investigate whether an exemplary nitro-fatty acid can limit atrial fibrosis and AF. Wild-type C57BL6/J mice were treated for 2 weeks with angiotensin II (AngII) and vehicle or nitro-oleic acid (10-nitro-octadec-9-enoic acid, OA-NO2, 6 mg/kg body weight) via subcutaneous osmotic minipumps. OA-NO2 significantly inhibited atrial fibrosis and depressed vulnerability for AF during right atrial electrophysiological stimulation to levels observed for AngII-naive animals. Left atrial epicardial mapping studies demonstrated preservation of conduction homogeneity by OA-NO2. The protection from fibrotic remodelling was mediated by suppression of Smad2-dependent myofibroblast transdifferentiation and inhibition of Nox2-dependent atrial superoxide formation. OA-NO2 potently inhibits atrial fibrosis and subsequent AF. Nitro-fatty acids and possibly other lipid electrophiles thus emerge as potential therapeutic agents for AF, either by increasing endogenous levels through dietary modulation or by administration as synthetic drugs.

Temporal Stability of Rotors and Atrial Activation Patterns in Persistent Human Atrial Fibrillation: A High-Density Epicardial Mapping Study of Prolonged Recordings

ObjectivesThis study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. BackgroundThe prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. MethodsEpicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm2; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n = 9) and the right atrial free wall (n = 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. ResultsThe dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. ConclusionsIn patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with short CL activity, and, when recurrent, demonstrate anatomical determinism.

WITHDRAWAL: Temporal Stability of Rotors and Atrial Activation Patterns in Persistent Human Atrial Fibrillation: A High-Density Epicardial Mapping Study of Prolonged Recordings

This study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. The prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. Epicardial mapping was performed in 10 patients undergoing cardiac surgery, with bipolar electrograms recorded over 10 min using a triangular plaque (area: 6.75 cm 2 ; 117 bipoles; spacing: 2.5 mm) applied to the left atrial posterior wall (n = 9) and the right atrial free wall (n = 4). Activations were identified throughout 6 discrete 10-s segments of AF spanning 10 min, and dynamic activation mapping was performed. The distributions of 4,557 generated activation patterns within each mapped region were compared between the 6 segments. The dominant activation pattern was the simultaneous presence of multiple narrow wave fronts (26%). Twelve percent of activations represented transient rotors, seen in 85% of mapped regions with a median duration of 3 rotations. A total of 87% were centered on an area of short CL activity (<100 ms), although such activity had a positive predictive value for rotors of only 0.12. The distribution of activation patterns and wave-front directionality were highly stable over time, with a single dominant pattern within a 10-s AF segment recurring across all 6 segments in 62% of mapped regions. In patients with longstanding, persistent AF, activation patterns are spatiotemporally stable over 10 min. Transient rotors can be demonstrated in the majority of mapped regions, are spatiotemporally associated with short CL activity, and, when recurrent, demonstrate anatomical determinism.

Temporal stability of rotors and atrial activation patterns in persistent human atrial fibrillation: A high density epicardial mapping study

Temporal stability of rotors and atrial activation patterns in persistent human atrial fibrillation: A high density epicardial mapping study

Temporal stability of the atrial fibrillation cycle length in persistent human atrial fibrillation and its relationship to drivers: a high density epicardial mapping study

Temporal stability of the atrial fibrillation cycle length in persistent human atrial fibrillation and its relationship to drivers: a high density epicardial mapping study

Fractionation of electrograms is caused by colocalized conduction block and connexin disorganization in the absence of fibrosis as AF becomes persistent in the goat model.

BackgroundElectrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear.ObjectiveThe aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change.MethodsOf 12 goats, atrial burst pacemakers maintained AF in 9 goats for up to 3 consecutive 4-week periods. After each 4-week period, 3 goats underwent epicardial mapping studies of the right atrium and examination of the atrial myocardium for immunodetection of connexins 43 and 40 (Cx43 and Cx40) and quantification of connective tissue.ResultsDespite refractoriness returning to normal in between each 4-week period of AF, there was a cumulative increase in the prevalence of fractionated atrial electrograms during both atrial pacing (control and 1, 2, and 3 months period of AF 0.3%, 1.3% ± 1.5%, 10.6% ± 2%, and 17% ± 5%, respectively; analysis of variance, P < .05) and AF (0.3% ± 0.1%, 2.3% ± 1.2%, 14% ± 2%, and 23% ± 3%; P < .05) caused by colocalized areas of conduction block during both pacing (local conduction velocity <10 cm/s: 0.1% ± 0.1%, 0.3% ± 0.6%, 6.5% ± 3%, and 6.9% ± 4%; P < .05) and AF (1.5% ± 0.5%, 2.7% ± 1.1%, 10.1% ± 1.2%, and 13.6% ± 0.4%; P < .05), associated with an increase in the heterogeneity of Cx40 and lateralization of Cx43 (lateralization scores: 1.75 ± 0.89, 1.44 ± 0.31, 2.85 ± 0.96, and 2.94 ± 0.31; P < .02), but not associated with change in connective tissue content or net conduction velocity.ConclusionElectrogram fractionation with increasing persistence of AF results from slow localized conduction or block associated with changes in atrial connexin distribution in the absence of fibrotic change.

Relationship among complex signals, short cycle length activity, and dominant frequency in patients with long-lasting persistent AF: A high-density epicardial mapping study in humans

Complex fractionated atrial electrograms (CFAEs) and regions of high dominant frequency (DF) both may identify sites critical to the maintenance of atrial fibrillation (AF). CFAEs may be defined by either (1) complex multicomponent electrograms (EGMs) and/or continuous electrical activity (multicomponent/continuous EGM) or (2) discrete high-frequency EGMs. The purpose of this study was to test if the 2 definitions of CFAE identify the same arrhythmia substrate and determine the relationship of CFAE to areas of high DF. High-density epicardial mapping of the posterior left atrium was performed in 10 patients with long-lasting persistent AF. Point-by-point analysis was performed to determine the spatial distribution and correlation of CFAE defined as either (1) multicomponent/continuous-EGMs or (2) AF cycle length <120 ms. Additionally, spatial analysis was performed to determine the relationship of high DF sites to CFAE sites defined by each of the 2 definitions. The percentage of sites deemed CFAE varied markedly between patients and was different depending on the definition of CFAE adopted. There was a poor correlation between CFAE defined by multicomponent/continuous EGMs and AF cycle length <120 ms (r = 0.18). High DF sites were arranged in clusters evenly distributed throughout the posterior left atrium, with 4.2 ± 1.0 high DF clusters per patient. Although there was poor point-by-point correlation between multicomponent/continuous EGMs and high DF sites (r = 0.107), spatial analysis revealed that 96% of multicomponent/continuous EGMs were found adjacent to and partially surrounding (≤5 mm) high DF sites. There is poor anatomic overlap between CFAE defined by multicomponent/continuous EGMs and CFAE defined by AF cycle length <120 ms. Multicomponent/continuous EGMs are found adjacent to and surrounding sites of high DF. Further studies are needed to determine the mechanisms responsible for these different signals.

Epicardial Left Ventricular Mapping Using Subxiphoid Video Pericardioscopy

We report a novel subxiphoid video pericardioscopy approach for epicardial mapping that allows direct visualization of the epicardium with minimal use of fluoroscopy. The FLEXview system (Boston Scientific Cardiac Surgery, Santa Clara, CA), which is capable of a free navigation around the heart owing to its flexible neck, was inserted into the pericardial space through a small subxiphoid incision. A commercially available mapping catheter advanced through the working port of the device could be navigated around virtually the entire biventricular epicardial surface. The subxiphoid video pericardioscopy approach using the FLEXview system provided adequate visualization and access to the epicardium of both ventricles for electroanatomic mapping while minimizing surgical invasiveness.

Normal Atrial Activation and Voltage During Sinus Rhythm in the Human Heart: An Endocardial and Epicardial Mapping Study in Patients with a History of Atrial Fibrillation

The three-dimensional contributions to human atrial activation in sinus rhythm have not been specifically characterized. We evaluated the sequence of endocardial and epicardial activation and voltage of the atria during normal sinus rhythm. The study group includes 35 patients with history of symptomatic atrial fibrillation. Prior to catheter ablation of atrial fibrillation, we performed multielectrode electroanatomic mapping during sinus rhythm, endocardially of the RA, LA, and coronary sinus (CS) and, in 10 patients, epicardially of the transverse sinus and oblique sinus. Following activation of the atrial region of the sinus node, the epicardial transverse sinus was activated 11 +/- 18 msec later, while the earliest endocardial LA activation occurred in the region of Bachmann's bundle at 31 +/- 13 msec, significantly earlier than the earliest epicardial LA activation of the oblique sinus at 54 +/- 10 msec (P < 0.002). The posterior LA revealed complex types of activation in 66% of patients analyzed, due to the convergence of wavefront propagation from the CS, oblique sinus, and endocardial LA. Bipolar voltage measurements revealed significantly higher values for the epicardium (mean 3.05 +/- 1.31 mv) than for the endocardium (mean 1.65 +/- 0.75 mv), P < 0.0001 between both groups. In sinus rhythm, we have characterized endocardial and epicardial atrial activation and voltage, and provide an analysis and understanding of the genesis of the P wave complex in humans.