A new approach for frequency analysis of complex fractionated atrial electrograms

Complex Fractionated Atrial Electrogram (CFAE) is associated with atrial fibrillation (AF) substrate. Culprit CFAE site might be pivot point of rotor wave. However, several sites with CFAE might behave just as bystander sites showing passive fibrillatory conduction. If AF termination is not obtained, is it no use ablating CFAE sites?CFAE ablation would eliminate fibrillatory conduction and help organizing AF, changing AF to atrial tachycardia (AT). CFAE might be related to the focus of driver (AT focus) or the site with activation gradient showing local reentry in small area. Therefore CFAE ablation would restore sinus rhythm in multi factorial ways. Recently important electrophysiological roles of ganglionated plexi (GP) have been emphasized. GP site is defined as showing parasympathetic response to high frequency stimulation. The sites of GP and CFAE are reported to overlap, however, details are unknown. We performed CFAE mapping by measuring fibrillation cycle length and displayed the sites of GP on that map. The result showed wide variety of fibrillation cycle length (30–176 ms) at the GP site. Although GP site may not demonstrate shortest fibrillation cycle length, GP site ablation eliminated AF inducibility in several cases, demonstrating GP is another important marker of AF substrate ablation, apart from CFAE ablation strategy.

The temporal variability of dominant frequency and complex fractionated atrial electrograms constrains the validity of sequential mapping in human atrial fibrillation

Different characteristics of complex fractionated atrial electrograms in acute paroxysmal versus long-standing persistent atrial fibrillation

The dominant morphology of fractionated atrial electrograms has greater temporal stability in persistent as compared with paroxysmal atrial fibrillation

Complex fractionated atrial electrograms (CFAEs) represent the electrophysiologic substrate for atrial fibrillation (AF). Progress in signal processing algorithms to identify CFAEs sites is crucial for the development of AF ablation strategies. Individual signal complexes in CFAEs reflect electrical activity of electrophysiologic substrate at given time. We developed a novel algorithm for automated search of individual signal complexes in CFAEs. This algorithm based on wavelet transform enables to describe CFAEs in a novel way and helps to classify CFAEs level of complexity (degree of fractionation). The method was tested using a representative set of 1.5s A-EGMs (n = 113) ranked by an expert into 4 categories: 1 -organized atrial activity; 2 -mild; 3 -intermediate; 4 -high degree of fractionation. Individual signal complexes were marked by an expert in every A-EGM in the dataset. This ranking was used as gold standard for comparison with the novel automatic search method. Following hit rates were achieved by performed automatic search on representative set of data: category 1: 100%, category 2: 98.2%, category 3: 92.06%, category 4: 63.89%. These results indicate that wavelet signal decomposition could carry high level of predictive information about the state of electrophysiologic substrate for AF.

Catheter ablation using radiofrequency energy has gained acceptance as an effective treatment for atrial fibrillation (AF). Several technical approaches have been developed that correspond to pathophysiological concepts of AF initiation and maintenance.Isolation of pulmonary veins is identified as the cornerstone of any ablation approach.The additional ablation of fragmented or complex ostial or nonostial potentials or left atrial linear ablation has been recently introduced to modify the substrate besides isolating the triggerin order to improve the success rate of AF ablation, especially in patients with persistent AF. In our non-randomized, single-center, observational study we evaluated the acute effects of complex fractionated atrial electrogram (CFAE) ablation guided by automated detection on dominant frequency (DF) and regulatory index (RI) for the fibrillatory process.The termination rate by CFAE ablation was low (12.5% in paroxysmal and 10% in persistent AF). Changes in DF and RI after CFAE ablation were not significant (<0.25 Hz and max. 0.02 increase for RI) in comparison with other ablation steps. Based on our results CFAE ablation guided by a dedicated software algorithm and performed after standard pulmonary vein isolation (PVI) without CFAE remapping does not influence the fibrillatory process significantly. By virtue of the latter CFAE mapping and ablation should be performed always after PVI. With introduction of additional extensive left atrial (LA) ablations the risk of complications have been increased. One of the most devastating complication of AF ablation is atrioesophageal fistula (AEF).Esophageal ulcerations (EU) have been proposed to be potential precursor lesions. In our large single-center study of more than 260 patients, we consistently screened patients for evidence of esophageal injury after AF ablation. In total, we found 2.2% of patients (6 of 267) presenting with EU. Parameters exposing a specific patient to risk of developing EU were persistent AF (5 of 95), additional lines performed (roofline: 6 of 114; LA isthmus: 4 of 49; coronary sinus: 5 of 66), and LA enlargement leading to sandwiching of the esophagus between the LA and thoracic spine. Multivariate analysis revealed LA-to-esophagus distance as the only significant risk factor. Not a single patient with PVI alone developed EU. With the use of a reasonable energy maximum of 25 W at the posterior LA wall using open irrigation catheters, we showed a low percentage of EU creation compared with other studies published. Identifying high-risk patients for esophageal injury 7 potentially has an impact on follow-up or treatment of these individuals by endoscopy or prophylactic treatment. In our substudy (including 31 patients) we assessed the acute effect of radiofrequency ablation (RFA) on distal esophageal acidity using leadless pH-metry capsules. We found that a significant number of patients (19.2%) undergoing RFA of AF develop pathologic acid reflux after ablation. In addition, a subgroup of patients (16.1%) has a preexisting condition of asymptomatic reflux prior to ablation. This finding may explain a potential mechanism for progression of esophageal injury to atrio-esophageal fistulas. We recommend a regular screening for EU in high-risk patients with an extensive lesion set and treatment with proton-pump inhibitor (PPI) medication if EU is discovered. Moreover prophylactic PPI treatment of all patients undergoing RFA of AF have to be considered.

High Dominant Frequencies and Fractionated Potentials Do Not Indicate Focal or Rotational Activation During AF

Background Diseased atria are characterised by functional and structural heterogeneities (e.g. dense fibrotic regions), which add to abnormal impulse generation and propagation, like ectopy and block. These heterogeneities are thought to play a role in the origin of complex fractionated atrial electrograms (CFAEs) under sinus rhythm (SR) in atrial fibrillation (AF) patients, but also in the onset and perpetuation (e.g. reentry) of this disorder. The underlying mechanisms, however, remain incompletely understood. Purpose To test the hypothesis that dense local fibrotic regions could create an electrically isolated conduction pathway in which reentry can be established via ectopy and block to become “trapped” (giving rise to CFAEs under SR), only to be “released” under dynamic changes at a connecting isthmus (causing acute focal arrhythmia (FA)). Methods The geometrical properties of such an electrically isolated pathway, under which reentry could be trapped and released, were explored in vitro using optogenetics by creating conduction blocks of any shape by means of light-gated depolarizing ion channels (CatCh) and patterned illumination. Insight from these studies was used for complementary computational investigation in virtual human atria to assess clinical translation and to provide deeper mechanistic insight. Results Optical mapping studies, in monolayers of CatCh-activated neonatal rat atrial cardiomyocytes, revealed that reentry could indeed be established and trapped by creating an electrically isolated pathway with a connecting isthmus causing source-sink mismatch. This proves that a tachyarrhythmia can exist locally with SR prevailing in the bulk of the monolayer. Next, it was confirmed under which conditions reentry could escape this pathway by widening of the isthmus (i.e. overcoming the source-sink mismatch), thereby converting this local dormant arrhythmic source into an active driver with global impact (i.e. acute monolayer-wide FA). This novel phenomenon was shown in circuits &amp;lt;0.7cm2, adding to their probability to exist in human atria. Computational 3D studies revealed that the conditions for “trapped reentry” and its release can indeed be realized in human atria. Unipolar epicardial pseudo-electrograms derived from these simulations showed CFAEs at the site of “trapped reentry” in coexistence with normal electrograms showing SR in the bulk of the atria. Upon release of the reentry through reduction of gap junctional coupling, acute FA occurred, affecting the complete atria as evidenced by wave front and electrogram visualization. Conclusion This study reveals that “trapped reentry”, a previously undesignated phenomenon, can explain the origin of two designated ones: the observation of CFAEs under SR and acute onset of FA. Further exploration of the concept of “trapped reentry” may not only expand our understanding of AF initiation and perpetuation, but also termination, including ablation strategies by site-directed targeting. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study was funded by the European Research Council (Starting grant 716509) to D.A. Pijnappels

Durability of wide-area left atrial appendage isolation: Results from extensive catheter ablation for treatment of persistent atrial fibrillation

Indices of bipolar complex fractionated atrial electrograms correlate poorly with each other and atrial fibrillation substrate complexity.

Background and purposeIn expectation of better outcome of catheter ablation of atrial fibrillation (AF), several strategies of extra‐PV (pulmonary vein) substrate modification have been utilized. We assessed whether substrate modification or ablation of extra‐PV source is a predictor of complications.MethodsJapanese Heart Rhythm Society requested electrophysiology centers to register the data of patients who underwent AF ablation.ResultsThe data of 10 795 AF ablation cases (age; 63.8 ± 10.6 years) treated during 2011‐2016 were registered. Pericardial effusion (n = 105), massive bleeding (n = 108), stroke (n = 6), atrial‐esophageal fistula (n = 2), and other 114 complications occurred in 323 patients (3.0%). Univariate analysis revealed that age ≧ 65 years, female gender, heart failure, CHA2DS2‐VASc≧3, hemodialysis, deep sedation, and complex fractionated atrial electrogram (CFAE)‐guided ablation ([+] vs [−] = 4.3% vs 2.8%, P = .005) were related with the higher incidence of complications. Redo session, 3‐D imaging system ([+] vs [−]: 4.4% vs 2.9%, P = .017), and periprocedural dabigatran were related with the lower incidence of complications. None of the linear ablation of the left atrium, ganglionated plexi ablation, and superior vena cava ablation affected the incidence of complications. Multiple logistic regression analysis showed that in addition to 3‐D imaging system, age ≧ 65 years, redo session, and deep sedation, CFAE ablation was an independent predictor of the risk of complications (OR 1.78, P = .001). Specifically, implantation of a permanent pacemaker due to emerging sinus node dysfunction was frequent after CFAE ablation (CFAE [+] vs [−] = 4/1047 vs 2/9748, P < .001).ConclusionsAmong extra‐PV ablation strategies, CFAE‐guided ablation is a predictor of ablation‐related complications.

Sites of complex fractionated atrial electrograms (CFAE) with a short mean cycle length (MCL) and sites with a high dominant frequency (DF) have been advocated as targets for ablation in patients with persistent atrial fibrillation (AF). However, there are little data on the relationship between theses 2 markers. This study assessed the relationship between the DF and electrogram MCL after pulmonary vein (PV) isolation in patients with persistent AF. A total of 44 patients with persistent AF were studied. Four-second bipolar electrograms were obtained with a multielectrode mapping catheter at regions throughout the left atrium after isolation of the pulmonary veins, with analysis of the MCL and DF at each site. The DF was defined as the largest frequency peak within a 2.5- to 16-Hz spectral profile generated with fast Fourier transformation of the electrogram. A total of 9,262 electrograms from the 44 patients were analyzed. The average MCL and DF post-PV isolation were 135 +/- 24 ms and 6.1 +/- 0.6 Hz, respectively. There was a statistically significant but weak correlation between the MCL and DF (r = 0.21, P < 0.001). Additionally, analysis of this relationship within each patient did not demonstrate a strong correlation (range of r values per patient =-0.18 to 0.47). There is a poor correlation between the electrogram MCL and DF in patients with persistent AF. Ablation strategies targeting DF and those targeting CFAE are therefore unlikely to direct ablation toward similar left atrial sites. Comparative studies are necessary to determine the effectiveness of each strategy in guiding catheter ablation of persistent AF.

Introduction We previously reported that patients (pts) with recurrence (Rec) after stepwise catheter ablation (step-CA) of persistent atrial fibrillation (pAF) exhibit high bi-atrial intracardiac dominant frequencies (DF) values before ablation, indicative of a severe bi-atrial electro-anatomical remodeling. Purpose Herein, we hypothesized that a gradual decrease in DF values during step-CA is associated with pAF termination and maintenance of sinus rhythm (SR) on the long term. Method In 40 consecutive pts (61±8 yo, sustained AF duration 19±11 months), pulmonary vein isolation (PVI) and left atrium (LA) ablation were performed until pAF termination or cardioversion. 10-sec intracardiac electrograms (EGMs) epochs were recorded before ablation (BL), during PVI and during complex fractionated atrial electrograms (CFAEs) and linear ablation (post_PVI) in the right atrial (RAA) and left atrial (LAA) appendages and in the coronary sinus (CS). DF was defined as the highest peak within the [3–15] Hz EGM spectrum. Rec was defined as any atrial arrhythmia lasting &gt;30 sec during follow-up (FU). Results pAF was terminated within the LA in 70% (28/40, LT) of the pts, while 30% (12/40, NLT) were not. After a mean FU of 34±14 months, all NLT pts had a Rec, while LT pts presented a Rec in 71% (20/28, LT_rec) and remained in SR in 29% (8/28, LT_norec). Figure 1 shows: 1) a gradient in DF values measured in the LAA (panel A), RAA (panel B) and CS (panel C) with the highest values in NLT pts (red), intermediate values in LT_rec pts (yellow) and lowest DF values in LT_norec pts (green); 2) all three groups displayed a gradual intracardiac organization during LA ablation as shown by decreasing DF values (p&lt;0.05, BL vs post_PVI), but the LT_norec pts (green) exhibited the highest relative changes in DF from BL (p&lt;0.05, LT_norec vs NLT, Δ range: −5.31 to −9.69%). Figure 1. Effect of ablation on DF Conclusion Low DF values before ablation and gradual intracardiac organization until pAF termination are associated with maintenance of SR on the long term.

Consistency of complex fractionated atrial electrograms during atrial fibrillation

Identification of complex fractionated atrial electrograms (CFAEs) sites is crucial for the development of new AF ablation strategies. CFAE may represent the electrophysiological substrate for atrial fibrillation (AF). Progress in signal processing algorithms is the key part of this task. Algorithm for automated description of atrial electrograms (A-EGMs) fractionation based on wavelet transform and several feature extraction methods and statistical pattern recognition was proposed and methodology of A-EGM processing was designed and tested. The algorithms for signal processing, description and classification were developed and validated using a representative set of 1:5 s A-EGMs (n = 113) ranked by 3 independent experts into 4 classes of fractionation: 1 – organized atrial activity; 2 – mild; 3 – intermediate; 4 – high degree of fractionation. The optimization algorithms for finding new feature extraction and classification algorithms are used and tested here. The performance of the optimization to find useful setup of A-EGM signal processing and classification is documented and showed. Mean classification error over all classes by more different algorithms varied from ~ 4 to ~ 8 %. Such fully automatic setups of algorithms for A-EGMs complexity description that do not need operator interaction may be easily incorporated into mapping systems to assist and guide AF substrate ablation.KeywordsAtrial fibrillationcatheter ablationcomplex fractionated atrial electrogramsclassificationoptimization