Electrophysiologic Characteristics of Complex Fractionated Atrial Electrograms in Patients with Atrial Fibrillation

Introduction: The underlying mechanisms of complex fractionated atrial electrogram (CFAE) during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) have not yet been clearly elucidated. We explored the relationships between CFAE and left atrial (LA) voltage, or conduction velocity (CV).
Methods and Results: In 50 patients with AF (23 paroxysmal AF [PAF], 41 males, mean age 55.76 ± 10.16 years), the CFAE (average index of fractionation of electrograms during AF by interval-analysis algorithm, cycle length [CL]≤ 120 ms) areas, voltage, and CV were measured at eight different quadrants in each patient's LA by analyzing a NavX-guided, color-coded CFAE CL map, a voltage map, and an isochronal map (500 ms pacing) generated by contact bipolar electrograms (70–100 points in the LA). The results were: (1) CFAE areas were predominantly located in the septum, roof, and LA appendage; (2) CFAE area had lower voltage than those in non-CFAE area and was surrounded by the areas of high voltage (P < 0.0001); (3) The CFAE areas had low CVs compared with non-CFAE areas (P < 0.001); and (4) The percentage of CFAE area was lower in patients with persistent atrial fibrillation (PeAF) compared with those with PAF (P < 0.05).
Conclusions: The CFAE area, which is primarily located at the septum, has a low voltage with a lower CV, and is surrounded by high-voltage areas. Underlying electroanatomical complexity is associated with clustering of CFAEs.     

Differences in organization between acute and chronic atrial fibrillation in dogs

OBJECTIVES: The purpose of this study was to determine differences in acute and chronic atrial fibrillation (AF) "organization" in canine models. BACKGROUND: Electrophysiologic changes occur during atrial remodeling, but little is known about how remodeling affects AF organization. We hypothesized that atrial remodeling induced by long-term rapid atrial rates heterogeneously decreases AF organization. METHODS: In seven dogs, acute AF was induced by atrial burst pacing, and in eight dogs chronic AF was created by six weeks of continuous rapid atrial pacing. Atrial fibrillation was epicardially mapped from the right atria (RA) and left atria (LA). Atrial cycle length (CL), spatial organization and activation maps were compared. Spatial organization was quantified by an objective signal processing measure between multiple electrograms. RESULTS In acute AF, mean CL was slightly shorter in the LA (124 +/- 16 ms) than it was in the RA (131 +/- 14 ms) (p < 0.0001). In chronic AF, LA CL (96 +/- 14 ms) averaged 24 ms shorter than RA CL (121 +/- 18 ms) (p < 0.0001). Right atria and LA in acute AF had similar levels of organization. In chronic AF, the LA became approximately 25% more disorganized (p < 0.0001) while the RA did not change. In acute AF, a single broad wave front originating from the posterior and medial atrium dominated LA activation. In chronic AF, LA activation was more complex, sustaining multiple reentrant wavelets in the free wall and lateral appendage. CONCLUSIONS: Acute and chronic AF exhibit heterogeneous differences in CL, organization and activation patterns. The LA in chronic AF is faster and more disorganized than it is in acute AF. Differences in the models may be due to heterogeneous electrophysiologic remodeling and anatomic constraints. The design of future AF therapies may benefit by addressing the patient specific degree of atrial remodeling.     

Automated detection and characterization of complex fractionated atrial electrograms in human left atrium during atrial fibrillation

BACKGROUND: Complex fractionated atrial electrograms (CFAEs) have been reported as ablative targets for the treatment of atrial fibrillation (AF). However, the process of CFAE identification is highly dependent on the operator's judgment. OBJECTIVE: It is the aim of the study to report our initial experience with a novel software algorithm designed to automatically detect CFAEs. METHODS: Nineteen patients (6 female, 58 +/- 8 years) who underwent catheter ablation of paroxysmal (n = 11) or persistent (n = 8) AF were included in the study. During ongoing AF, 100 +/- 15 left atrial (LA) endocardial locations were sampled under the guidance of integrated electroanatomical mapping with computed tomographic images. Bipolar electrograms recorded throughout the LA were analyzed using custom software that allows for automated detection of CFAEs. Interval confidence level (ICL), defined as the number of intervals between consecutive CFAE complexes during 2.5-second recordings, was used to characterize CFAEs. The CFAE sites with an ICL >/=5 were considered as sites with highly repetitive CFAEs, which are thought to be potential ablation targets. For purposes of analysis, the LA was divided into 6 areas: pulmonary vein (PV) ostia, posterior wall, interatrial septum, roof, mitral annulus area, and appendage. RESULTS: Among a total of 1,904 LA locations sampled in 19 patients, 1,644 (86%) were categorized as CFAE sites, whereas 260 (14%) were categorized as as non-CFAE sites. Thirty-four percent of all CFAE sites were identified as sites with highly repetitive CFAEs. Of these, 24% were located at the interatrial septum, 22% on the posterior wall, 20% at the PV ostia, 18% at the mitral annulus area, 14% on the roof, and 2.7% at the LA appendage. In all patients, highly repetitive CFAE sites were distributed in 4 or more areas of the LA. Persistent AF patients had more highly repetitive CFAE sites on the posterior wall than paroxysmal AF patients (30% +/- 7.3% vs 14% +/- 8.2%, P < .001). There was a strong trend toward more highly repetitive CFAE sites located at the PV ostia in patients with paroxysmal AF compared with persistent AF patients (24% +/- 13% vs 13% +/- 7.7%, P = .05). CONCLUSION: With the use of custom software, CFAE complexes were identified in more than 80% of the LA endocardial locations. LA sites with highly repetitive CFAE sites were located predominately in the septum, posterior wall, and PV ostia. Patients with persistent AF had a different anatomical distribution pattern of highly repetitive CFAE sites from those with paroxysmal AF, with a greater prevalence of highly repetitive CFAEs located on the posterior wall. Further studies are warranted to determine the clinical significance of these findings.     

持续性心房颤动山羊模型的心房单极电极标测

在持续性心房颤动 (简称房颤 )山羊模型上 ,研究心房不同部位房颤周长 (AFCL)及单极心外膜电图的差异 ,并利用激动标测图分析房颤时的蝉联现象。将 83个电极分别缝合于 7只山羊的左心房游离壁、左心耳、Bachmann束 (BB)、右心耳游离壁的心外膜。利用自动房颤刺激器维持房颤 ,待房颤持续 4周后 ,取 16s的心外膜电图作分析。利用单极电图标记局部激动时间 ,并根据单极电图的形态特点将其标记为正常电位 (单电位和短的双电位 )及异常电位 (长的双电位、三电位及碎裂电位 )。根据左心房局部激动时间重建等电位激动标测图 ,如超过 7次连续心房搏动经过相同路径 ,则定义为蝉联片段。在左心房、左心耳、BB、右心耳及右心房的AFCL分别为 94 .9± 4 .6 ,95 .7±4 .4 ,10 5 .7± 6 .5 (与其他部位比较 ,P <0 .0 5 ) ,99.2± 8.0及 98.5± 6 .3ms ;异常电位的百分比分别为 2 0 .9%± 6 .3% ,2 7.8%± 11.8% ,5 7.4 %± 7.8% (与其他部位比较 ,P <0 .0 1) ,18.6 %± 9.7%和 19.4 %± 3.9%。在所记录的 16s房颤过程中 ,左心房共有 70 5次心搏 ,其中 6 8次 (9.6 % )属于蝉联片段。结论 :在山羊持续房颤模型 ,BB的AFCL最长 ,异常电位的发生率最高 ,提示BB在房颤的维持上起重要作用。蝉联现象的存在表明房颤时心房激动并     

Atrial Fibrillatory Wall Motion and Degree of Atrial Remodeling in Patients with Atrial Fibrillation: A Tissue Velocity Imaging Study

Introduction: The atrial fibrillation cycle length (AFCL) and the intracardiac atrial electrogram morphology may be used to characterize atrial fibrillation (AF). However, assessment of these parameters requires an invasive electrophysiological study. We assessed clinical and electrophysiological correlates of noninvasive tissue velocity imaging (TVI) of the right and left atrial myocardial fibrillatory wall motion. Methods and Results: We performed an electrophysiological study in 12 patients with AF referred for His bundle ablation. Using atrial electrograms, we determined the AFCL (AFCL‐egm) and electrophysiological AF type. Simultaneously, transthoracic echocardiography was performed. We used the TVI traces to determine the cycle length of the atrial fibrillatory wall motion (AFCL‐tvi) and atrial fibrillatory wall velocities (AFV‐tvi). AFCL‐tvi matched very well with AFCL‐egm (r²= 0.98; P < 0.001), both in the left and right atrium. Patients with permanent AF had shorter AFCL‐tvi (155 ± 15 ms vs 216 ± 23 ms; P < 0.001), higher AFCL‐tvi variability, and lower AFV‐tvi compared to patients with paroxysmal AF. Three electrophysiological AF types were found based on the morphology of the electrograms and these related to specific TVI patterns. Conclusion: TVI of the atrial fibrillatory wall motion may enhance noninvasive characterization of atrial remodeling in patients with atrial fibrillation.     

Electrophysiology and endocardial mapping of induced atrial fibrillation in patients with spontaneous atrial fibrillation

We analyzed the patterns of atrial activation and characterized the electrophysiologic properties of regional atrial sites in the, right atrium and left atrium at the onset of atrial fibrillation (AF) induced with programmed right atrial (RA) stimulation. Intraatrial conduction, atrial electrogram return cycle lengths for the first AF cycle, RA and left atrial (LA) activation maps during AF, and the stability and reproducibility of atrial activation sequences at AF onset and maintenance were analyzed in 23 patients with AF. Correlation of intracardiac electrograms with surface electrocardiographic morphology was attempted. Maximum intraatrial conduction delay for high RA premature beats was observed at the coronary sinus ostium (n = 15), His bundle region (n = 13) or interatrial septum (n = 15). The return cycle lengths for the first AF cycle showed increasing conduction delay with increasing prematurity of the last extrastimulus in most patients. Suprisingly, discrete atrial electrograms with regular or irregular cycle lengths were present at the onset of electrocardiographic documented coarse AF in 13 of 15 patients (87%). Fragmented or chaotic atrial activity were present in 2 of 15 patients (13%) in coarse AF but observed at > or = 1 atrial sites in 7 of 8 patients (88%) with fine AF (p = 0.001). The atrial activation sequence at the onset of the induced AF elicited by high RA extrastimuli usually showed the earliest activation site at the crista terminalis (9 patients) or interatrial septum (9 patients). In contrast, induced AF elicited from other RA sites usually showed earliest atrial activation at the septum (3 patients) or coronary sinus ostium (3 patients). Atrial activation sequences for the first induced AF cycle were usually reproducible in most patients. Atrial activation patterns during the first 10 cycles for AF were stable in RA and LA regions in 6 of 23 patients (260%) but demonstrated significant change(s) at > or = 1 region in 17 of 23 patients (74%) (p <0.05). We conclude that pacing induced AF elicited by RA premature beats commences as a regular or irregular rapid atrial tachycardia consistent with a transitional, but often organized, arrhythmia. The activation sequence and electrophysiologic behavior of the first induced AF cycle is consistent with intraatrial reentry and reproducible in most patients. More than 1 atrial activation sequence can sometimes be observed, emphasizing the dynamic nature of the initial RA reentrant circuits.     

Consistency of complex fractionated atrial electrograms during atrial fibrillation

BACKGROUND: Temporal variation in complex fractionated atrial electrograms (CFAEs) exists during atrial fibrillation (AF). OBJECTIVE: This study sought to quantify the variation in CFAEs using a fractionation interval (FI) algorithm and to define the shortest optimal recording duration required to consistently characterize the magnitude of the fractionation. METHODS: Twenty-seven patients undergoing AF mapping in the left atrium were studied. The FI and frequency analysis were performed at each mapped site for recording durations of 1 to 8 seconds. The magnitude of the fractionation was quantified by the FI algorithm, which calculated the mean interval between multiple, discrete deflections during AF. The results from each duration were statistically compared with the maximal-duration recording, as a standard. The FI values were compared with the dominant frequency values obtained from the associated frequency spectra. RESULTS: The FIs obtained from recording durations between 5 and 8 seconds had a smaller variation in the FI (P < .05) and, for those sites with a FI < 50 ms, the fractionation was typically continuous. The fast-Fourier Transform spectra obtained from the CFAE sites with recording durations of >5 seconds harbored higher dominant frequency values than those with shorter recording durations (8.1 +/- 2.5 Hz vs. 6.8 +/- 0.98 Hz, P < .05). The CFAE sites with continuous fractionation were located within the pulmonary veins and their ostia in 77% of patients with paroxysmal AF, and in only 29% of patients with nonparoxysmal AF (P < .05). CONCLUSION: The assessment of fractionated electrograms requires a recording duration of > or =5 seconds at each site to obtain a consistent fractionation. Sites with the shortest FIs consistently identified sites with the fastest electrogram activity throughout the entire left atrium and pulmonary veins.     

Automatic 3D mapping of complex fractionated atrial electrograms (CFAE) in patients with paroxysmal and persistent atrial fibrillation

Background: Complex fractionated atrial electrograms (CFAE) are a possible target for atrial fibrillation (AF) ablation and can be visualized in three‐dimensional (3D) mapping systems with specialized software. Objective: To use the new CFAE software of CartoXP® (Biosense Webster, Diamond Bar, CA, USA) for analysis of spatial distribution of CFAE in paroxysmal and persistent AF. Methods: We included 16 consecutive patients (6 females; mean 59.3 years) with AF (6 paroxysmal and 10 persistent) undergoing AF ablation. Carto maps of left atrium (LA) were reconstructed. Using the new CFAE software, the degree of local electrogram fractionation was displayed color‐coded on the map surface. LA was divided into four regions: anterior wall, inferior wall, septum, and pulmonary veins (PV). The relationship among regions with CFAE visualized and CFAE ablation regions (persistent AF only) was analyzed retrospectively. Results: In paroxysmal and persistent AF, CFAE were observed in all four LA regions. In paroxysmal AF, the density of CFAE around the PV was significantly higher than in other regions (P < 0.05) and higher than in persistent AF (P < 0.05). In persistent AF, CFAE were evenly distributed all over the LA. Of 40 effective ablation sites with significant AF cycle length prolongation, 33 (82.5%) were judged retrospectively by CFAE map as CFAE sites. Conclusion: CFAE software can visualize the spatial distribution of CFAE in AF. CFAE in persistent AF were observed in more regions of LA compared to paroxysmal AF in which CFAE concentrated on the PV. Automatically detected CFAE match well with ablation sites targeted by operators.     

The effect of electrogram duration on quantification of complex fractionated atrial electrograms and dominant frequency

Introduction: Sites of complex fractionated atrial electrograms (CFAEs) and highest dominant frequency (DF) have been proposed as critical regions maintaining atrial fibrillation (AF). This study aimed to determine the minimum electrogram recording duration that accurately characterizes CFAE or DF sites for ablation without unduly lengthening the procedure.
Methods and Results: Fourteen patients with AF undergoing catheter ablation had high-density (498 ± 174 points) biatrial mapping performed during AF before ablation. At each point, 8-second electrograms were recorded. CFAE characterization using the NavX software provided a representation of electrogram complexity (CFE-mean). CFE-mean for each point from 7-, 6-, 5-, 4-, 3-, 2-, and 1-second subsamples were compared with the index 8-second CFE-mean. Offline spectral analysis defined DF as the frequency with greatest power, and DF of subsamples were compared with index DF. Index 8-second electrogram CFE-mean was 114 ± 20 ms for right atria and 102 ± 17 ms for left atria (P = 0.01); DF was 5.7 ± 0.8 Hz for right atria and 6.0 ± 0.8 Hz for left atria (P = 0.02). Means from shorter electrograms were nonsignificantly decreased for CFE-mean and overestimated for DF (P < 0.001). Mean absolute differences between subsampled and index values ranged from 3.3 to 20.1 ms for CFE-mean and 0.11 to 1.18 Hz for DF. Subsampled electrograms deviating >10% from index values ranged from 2.5 to 56% for CFE-mean and 3.5 to 41% for DF. Intraclass correlation coefficients ranged from 0.992 to 0.788 for CFE-mean and 0.897 to 0.233 for DF. Unacceptable differences from index values were found with CFE-mean and DF from electrograms <5 seconds.
Conclusion: Electrograms of ≥5-second duration are required to accurately characterize CFAE and DF sites for ablation.     

A prospective, multicenter evaluation of ablating complex fractionated electrograms (CFEs) during atrial fibrillation (AF) identified by an automated mapping algorithm: Acute effects on AF and efficacy as an adjuvant strategy

BACKGROUND: Complex fractionated electrograms (CFEs) are continuous electrograms (EGMs) of very short cycle length (CL) representing substrate for atrial fibrillation (AF) perpetuation. Ablation of CFEs may result in AF slowing, termination, and prevention, but identifying them can be subjective. OBJECTIVE: The purpose of this study was to prospectively assess (1) whether an automated algorithm can identify CFE regions, (2) the acute effects of ablating these regions on AF, and (3) the long-term efficacy as an adjuvant strategy to pulmonary vein antrum isolation (PVAI). METHODS: Thirty-five patients (three centers, 61 +/- 9 years, left atrium [LA] 43 +/- 9 mm, ejection fraction 53% +/- 7%) with symptomatic paroxysmal (n = 21) or persistent (n = 14) AF were studied. A decapolar lasso (2-mm spacing) was used for mapping. A three-dimensional shell of the LA and pulmonary veins (PVs) was created. If not already in AF, AF was induced by burst pacing (with or without isoproterenol). Atrial EGMs during AF were mapped/analyzed using an automated CFE algorithm. The algorithm measures the time between discrete deflections in a local EGM over 5 seconds (based on selectable width and peak-to-peak [>0.03 mV] criteria). The mean CL of the local EGM is projected onto the LA shell as a color-coded display. Regions of CL <120 ms (published criteria) were targeted for ablation/elimination. Atrial fibrillation cycle length (AFCL) and regularity were measured from the CS. After CFE ablation, further ablation was done to achieve complete PVAI. RESULTS: AF was spontaneous (n = 20) or induced (n = 15) in all patients. CFEs were most commonly found along the septum (97%), anterior LA (97%), PV antra (83%), base of appendage (83%), and annulus (71%). CFE ablation alone prolonged the AFCL (171 +/- 27 vs. 304 +/- 41 ms; P = .03) and regularized AF to left/right flutter (AFL) in 74% of patients. CFE ablation terminated AF/AFL in 19 patients (54%)-the other 16 were cardioverted-and AF became noninducible in 77%. CFE ablation alone did not cause PV isolation (0.1 +/- 0.3 PV isolated/patient). After combined CFE and PVAI ablation, the single-procedure, off-drug success rate was 83% (follow-up 13 +/- 4 months) versus 71% in matched controls who had PVAI alone (P = .045). CONCLUSIONS: CFE ablation guided by an automated algorithm resulted in AFCL prolongation, regularization, and noninducibility in most patients. AF terminated in 54% of cases. PVAI with adjuvant CFE ablation has a high efficacy and may be superior to PVAI alone.     

Prolonged fractionation of paced right atrial electrograms in patients with atrial flutter and fibrillation

OBJECTIVES: This study investigated the extent of fractionation of paced right atrial electrograms in patients with and without paroxysmal atrial flutter (AFL) or atrial fibrillation (AF). BACKGROUND: Slow conduction through nonuniform anisotropic atrial muscles, represented by fractionated electrograms, may favor the generation of atrial tachyarrhythmias. METHODS: This study included 10 control patients (Group 1), 8 patients with documented paroxysmal AFL (Group 2) and 10 patients with documented paroxysmal AF (Group 3). Five electrode catheters were placed in the different sites of the right atrium and one catheter was positioned at the coronary sinus ostium. Atrial pacing from one site was done by a constant drive train with an extrastimulus inserted every fourth beat while recording at the other five sites was performed. The delay of each fractionated potential in the high-pass filtered atrial electrogram in response to extrastimulation was determined and used to construct conduction curves of delay versus the S1S2 interval. RESULTS: The mean increase in electrogram duration between a coupling interval of 350 ms and 10 ms above atrial refractoriness was significantly greater in Groups 2 and 3 compared with that in Group 1 (8.5 +/- 2.5 vs. 11.0 +/- 2.7 vs. 5.9 +/- 2.3 ms, respectively, p < 0.001). The mean S1S2 interval at which delay increased suddenly was also longer in Groups 2 and 3 compared with Group 1 (326 +/- 9 vs. 343 +/- 12 vs. 307 +/- 17 ms, respectively, p < 0.001). CONCLUSIONS: Increased delays in the individual potential of the fractionated atrial electrograms may be related to the development of AFL and AF.     

The Optimal Automatic Algorithm for the Mapping of Complex Fractionated Atrial Electrograms in Patients With Atrial Fibrillation

CFAEs and the Voltage.   Introduction: Catheter ablation of atrial fibrillation (AF) can be guided by the identification of complex fractionated atrial electrograms (CFAEs). We aimed to study the prediction of the CFAEs defined by an automatic algorithm in different atrial substrates (high voltage areas vs low voltage areas).
Methods and Results: This study included 13 patients (age = 56 ± 12 years, paroxysmal AF = 8 and persistent AF = 5), who underwent mapping and catheter ablation of AF with a NavX system. High-density voltage mapping of the left atrium (LA) was performed during sinus rhythm (SR) (248 ± 75 sites per patient) followed by that during AF (88 ± 24 sites per patient). The CFAE maps were based on the automatic-detection algorithm. "Operator-determined CFAEs" were defined according to Nademannee's criteria. A low-voltage zone (LVZ) was defined as a bipolar voltage of less than 0.5 mV during SR. Among a total of 1150 mapping sites, 459 (40%) were categorized as "operator-determined CFAE sites," whereas 691 (60%) were categorized as "operator-determined non-CFAE sites." The sensitivity and negative predictive value increased as the fractionated interval (FI) value of the automatic algorithm increased, but the specificity and positive predictive value decreased. The automatic CFAE algorithm exhibited the highest combined sensitivity and specificity with an FI of <60 ms for the sites inside the LVZ and FI < 70 ms for the sites outside the LVZ, when compared with a single threshold for both the high- and low-voltage groups combined (i.e., no regard for voltage) (ROC: 0.89 vs 0.86).
Conclusions: The clinical relevance of the CFAE map would be improved if the calculated index values were accordingly scaled by the electrogram peak-to-peak amplitude. (J Cardiovasc Electrophysiol, Vol. 21, pp. 21–26, January 2010)     

Long-term changes in sequence of atrial activation and refractory periods: no evidence for "atrial memory".

OBJECTIVES: The purpose of this study was to test whether the spatial distribution of the atrial refractory period (AERP) and the vulnerability to atrial fibrillation (AF) are altered by long-term changes in the sequence of atrial activation. BACKGROUND: The spatial distribution of the AERP plays an important role in AF. Changes in the activation sequence have been postulated to modulate atrial repolarization ("atrial memory"). METHODS: Six goats were chronically instrumented with epicardial atrial electrodes to determine activation time and AERP at 11 different areas of the right (RA) and left (LA) atrium and the Bachmann bundle. Activation time and AERP were measured during sinus rhythm and during prolonged RA and LA pacing (1 week RA pacing, 2 weeks LA pacing, 1 week RA pacing; 150 bpm). Inducibility of AF was determined by the number of atrial sites where single premature stimuli induced AF paroxysms >1 second. RESULTS: During sinus rhythm (106 +/- 4 bpm), AERP was longest at the Bachmann bundle and shortest at the LA free wall (185 +/- 6 ms and 141 +/- 5 ms, P < .001). In five of six goats, an inverse correlation between local activation time and AERP was found during sinus rhythm (r = -0.53 +/- 0.05; P < .05). The increase in atrial rate during RA and LA pacing caused an overall shortening of AERP from 167 +/- 6 ms to 140 +/- 6 ms (P < .001). However, a switch between long-term RA and LA pacing did not significantly change AERP at any of the 11 atrial regions and had no significant effect on AF inducibility. CONCLUSIONS: During sinus rhythm, an inverse relationship exists between the sequence of atrial activation and the local refractory period. However, long-term changes in the sequence of atrial activation do not alter the spatial distribution of AERP or the inducibility of AF.     

Impact of Pharmacological Autonomic Blockade on Complex Fractionated Atrial Electrograms

Autonomic Blockade During Atrial Fibrillation . Introduction: The influence of the autonomic nervous system on the pathogenesis of complex fractionated atrial electrograms (CFAE) during atrial fibrillation (AF) is incompletely understood. This study evaluated the impact of pharmacological autonomic blockade on CFAE characteristics. Methods and Results: Autonomic blockade was achieved with propanolol and atropine in 29 patients during AF. Three‐dimensional maps of the fractionation degree were made before and after autonomic blockade using the Ensite Navx^® system. In 2 patients, AF terminated following autonomic blockade. In the remaining 27 patients, 20,113 electrogram samples of 5 seconds duration were collected randomly throughout the left atrium (10,054 at baseline and 10,059 after autonomic blockade). The impact of autonomic blockade on fractionation was assessed by blinded investigators and related to the type of AF and AF cycle length. Globally, CFAE as a proportion of all atrial electrogram samples were reduced after autonomic blockade: 61.6 ± 20.3% versus 57.9 ± 23.7%, P = 0.027. This was true/significant for paroxysmal AF (47 ± 23% vs 40 ± 22%, P = 0.003), but not for persistent AF (65 ± 22% vs 62 ± 25%, respectively, P = 0.166). Left atrial AF cycle length prolonged with autonomic blockade from 170 ± 33 ms to 180 ± 40 ms (P = 0.001). Fractionation decreases only in the 14 of 27 patients with a significant (>6 ms) prolongation of the AF cycle length (64 ± 20% vs 59 ± 24%, P = 0.027), whereas fractionation did not reduce when autonomic blockade did not affect the AF cycle length (58 ± 21% vs 56 ± 25%, P = 0.419). Conclusions: Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not persistent AF. This effect appears to be mediated by prolongation of the AF cycle length. (J Cardiovasc Electrophysiol, Vol. pp. 766‐772, July 2010)     

心房可兴奋间期对山羊心房颤动稳定性的影响

目的研究山羊心房可兴奋间期(EP)在心房颤动(房颤)稳定过程中的作用。方法在10只山羊的左心房游离壁外膜缝合电极片,利用自制的房颤刺激器于体外发放50HZ的刺激1S,每次间隔2S,诱发维持时间超过24H的持续性房颤。定期终止刺激,记录房颤自发持续时间,计算平均房颤波周长(AFCL),并在房颤持续过程中利用感知房颤波发放刺激夺获心房的方法测量房颤时心房有效不应期(ERPAF),计算EP(EP=AFCL-ERPAF)。结果8只山羊完成实验,均在6~16(9·3±4·6)D内诱发出持续超过24H的持续性房颤。在房颤自发维持达3~10MIN和24H时的AFCL分别为98·3MS±11·0MS与84·9MS±5·2MS,P<0·05;ERPAF分别为90·5MS±13·2MS与63·0MS±4·8MS,P<0·05;EP分别为7·8MS±2·4MS与21·9MS±3·5MS,P<0·05。结论心房ERPAF的缩短大于AFCL的缩短,使得EP持续性增宽,可能在房颤的稳定过程中起重要作用。     

Regional endocardial mapping of spontaneous and induced atrial fibrillation in patients with heart disease and refractory atrial fibrillation.

We performed simultaneous catheter mapping of right and left atrial regions at onset and during sustenance of spontaneous atrial fibrillation (AF) in patients with ischemic and/or hypertensive heart disease. Seventeen patients with structural heart disease had spontaneous and electrically induced AF episodes mapped from their onset simultaneously in multiple right and left atrial regions. Atrial premature complexes (APCs) that initiated spontaneous AF had coupling intervals ranging from 260 to 400 ms (mean 332 +/- 61), most commonly arising from the lateral right atrium (31%), right atrioventricular junction (13%), atrial septum (6%), superior left atrium (25%), or inferior left atrium (25%). APC morphology on surface electrocardiograms did not correlate with origin in specific atrial regions. The earliest regions of atrial activation for the first AF cycle were the lateral right atrium (n = 5), superior left atrium (n = 4), distal or mid coronary sinus (n = 4), atrial septum (n = 2), and right atrioventricular junction at the His bundle location (n = 2). Spontaneous AF at onset usually showed discrete but irregular electrograms at virtually all right and left atrial sites mapped, with a reproducible region of AF initiation in all 8 patients with multiple events. The region of earliest atrial activation at spontaneous AF onset was in close proximity to the APC origin in 15 of 16 patients (94%), and 39 of 40 episodes (97%) mapped. Stable patterns of right and left atrial activation were observed at AF onset in 14 patients. Induced AF elicited with right atrial stimulation demonstrated different sites of earliest regional atrial activation at onset compared with spontaneous AF events in 4 of 8 patients. However, discrete intracardiac electrograms were also present in induced AF in all of the mapped atrial regions. Furthermore, the site of extrastimulus delivery in induced AF was also found to be in close proximity to the earliest region of atrial activation for the first AF beat. We conclude that spontaneous AF is initiated by APCs arising in different right or left atrial regions in patients with structural heart disease and the initial region of atrial activation in AF is in proximity to the region of APC origin. Organized and repetitive electrical activation is frequently observed in both right and left atria at AF onset. Although electrically induced AF may have different activation patterns than spontaneous AF at onset in many patients, both types of AF demonstrate organization and earliest atrial activation in proximity to the initiating APC.     

犬快速心房起搏心房颤动模型全心房心外膜标测以及静脉胺碘酮对其心电的影响

探讨快速心房起搏心房颤动(简称房颤)模型房颤发作时肺静脉、左右心房各部位激动频率的差异以及胺碘酮对其电生理特性的影响。选健康雄性杂种犬10只,以400次/分的固定频率进行右心耳起搏,建立快速心房起搏房颤模型。10周后终止起搏,行64道全心房心外膜标测。标测部位分别为左右心房游离壁、左右心房顶部、左上肺静脉、左下肺静脉、右上肺静脉和右下肺静脉。记录以上部位的心外膜电图,测量各标测部位的平均房颤波周长(AFCL),并对不同部位心外膜标测电图进行频谱分析。静脉注射胺碘酮300mg,分析胺碘酮治疗前后各部位有效不应期(ERP)和AFCL的变化。结果:8只犬完成整个实验。在所有8只犬中,最短AFCL/ERP位于Marshall韧带的有2只,位于左下肺静脉的有6只;AFCL/ERP在心房的分布呈明显的梯度分布,自短至长依次为:肺静脉或Marshall韧带、左房游离壁和左侧Bachmann束、右侧Bachmann束和右房游离壁;频谱分析结果与AFCL分析结果一致;胺碘酮虽然可延长肺静脉和心房各部位ERP和AFCL,但是不能终止房颤的发作。结论:局灶机制可能是快速心房起搏房颤模型的发生和维持机制。     

普罗帕酮转复山羊持续性心房颤动过程中左上肺静脉和左房外膜电图的变化

目的研究普罗帕酮转复心房颤动(简称房颤)时左上肺静脉(LSPV)和左房(LA)外膜电图的变化,分析普罗帕酮转复房颤的可能机制。方法在6只山羊的LA前壁及LSPV根部外膜缝合电极片,LA快速刺激诱发房颤,在房颤自发维持超过24h后,静脉滴注普罗帕酮直至房颤终止。分析用药前、后房颤波周长(AFCL)分别延长40,80ms和房颤转复前各16s的间期内,LSPV和LA外膜电图的变化规律。结果6只山羊在经过静脉滴注普罗帕酮后,全部转复为窦性心律。用药前的LSPV的AFCL显著短于LA(P<0.05);用药后LSPV和LA的AFCL都出现逐渐延长,在房颤转复前两者趋于一致。用药前LSPV双电位和碎裂电位的百分比显著高于LA,单电位比例显著低于LA(P<0.05);用药后,LA和LSPV单电位百分比逐渐增加,双电位和碎裂电位逐渐减少,但在LA双电位和碎裂电位的比例始终小于LSPV(P<0.05);在房颤终止前LA先于LSPV出现双电位和碎裂电位的显著减少或消失,当LSPV的双电位和碎裂电位消失后房颤才终止。结论在本模型中,普罗帕酮对左房、肺静脉电生理的影响在房颤的转复过程中起着重要的作用。     

Atrial Electrograms and Activation Sequences in the Transition Between Atrial Fibrillation and Atrial Flutter

Transition Between Atrial Fibrillation and Flutter. Introduction: The eletrophysiologic mechanism of atrial fibrillation (AF) has a wide spectrum, and it seems that some atrial regions are essential for the occurrence of a particular type of AF. We focused on one type of AF: AF associated with typical atrial flutter (AFI), which was right atrial (RA) arrhythmia, and sought to investigate intra-atrial electrograms and activation sequences in the transition between AF and AFL.
Methods and Results: Intra-atrial electrograms and activation sequences in the R.A free wall and the septum were evaluated in the transition between AF and AFL in seven patients without organic heart disease (all men; mean age 57 ± 11 years). In five episodes of the conversion of AFL into AF, the AFL cycle length was shortened (from 211 ± 6 msec in stable AFL to 190 ± 15 msec before the conversion, P, 0.001). Interruption of the AFL wavefront and an abrupt activation sequential change induced by a premature atrial impulse resulted in fractionation and disorganization of the septal electrograms. During sustained AF, septal electrograms were persistently fractionated with disorganized activation sequences. However, the RA free-wall electrograms were organized, and the activation sequence was predominantly craniocaudal rather than caudocranial throughout AF. In 12 episodes of the conversion of AF into AFL, the AF cycle length measured in the RA free wall increased (from 165 ± 26 msec at the onset of AF to 180 ± 24 msec before the conversion, P, 0.001). AFL resumed when fractionated septal electrograms were separated and organized to the caudocranial direction, despite the RA free-wall electrograms remaining discrete and sharp with an isoelectric line.
Conclusion: Changes of the electrogram and activation sequence in the atrial septum played an important role in the transition between AF and AFL.     

Chronic atrial dilation, electrical remodeling, and atrial fibrillation in the goat.

OBJECTIVES: This study was designed to investigate the mutual effects of chronic atrial dilation and electrical remodeling on the characteristics of atrial fibrillation (AF). BACKGROUND: Both electrical remodeling and atrial dilation promote the inducibility and perpetuation of AF. METHODS: In seven goats AF was induced during 48 h by burst pacing, both at baseline and after four weeks of slow idioventricular rhythm (total AV block). Atrial size and refractory period (AERP) were monitored together with the duration and cycle length of AF paroxysms (AFCL). After four weeks of total atrioventricular (AV) block, the conduction in both atria was mapped during AF. Six non-instrumented goats served as controls. RESULTS: At baseline, AF-induced electrical remodeling shortened AERP and AFCL to the same extent (from 185 +/- 9 ms to 149 +/- 14 ms [p < 0.05] and from 154 +/- 11 ms to 121 +/- 5 ms [p < 0.05], respectively). After four weeks of AV block the right atrial diameter had increased by 13.2 +/- 3.0% (p < 0.01). Surprisingly, in dilated atria electrical remodeling still shortened the AERP (from 165 +/- 9 ms to 132 +/- 15 ms [p < 0.05]) but failed to shorten the AFCL (140 +/- 19 ms vs. 139 +/- 11 ms [p = 0.98]). Mapping revealed a higher incidence of intra-atrial conduction delays during AF. Histologic analysis showed no atrial fibrosis but did reveal a positive correlation between the size of atrial myocytes and the incidence of intra-atrial conduction block (r = 0.60, p = 0.03). CONCLUSIONS: In a goat model of chronic atrial dilation, AF-induced electrical remodeling was unchanged. However, AFCL no longer shortened during electrical remodeling. Thus, in dilated atria a wider excitable gap exists during AF, probably caused by intra-atrial conduction defects and a higher contribution of anatomically defined re-entrant circuits.