An Evaluation of Phase Analysis to Interpret Atrial Activation Patterns during Persistent Atrial Fibrillation for Targeted Ablation.

BACKGROUND: Phase analysis has been used to identify and localize atrial fibrillation (AF) sources for targeted ablation. We previously demonstrated that repetitive wannabe reentry (incomplete reentry) often generated an apparent stable rotor using phase analysis. The misinterpretation caused by phase analysis using atrial electrograms (AEGs) may result from detecting inaccurate time points at phase inversion (π to -π) in the instantaneous phase waveform converted from AEG. The purpose of this study was to evaluate the accuracy of phase analysis to detect atrial activations recorded from the high-density mapping of AF in patients with persistent and long-standing persistent (LSP) AF. METHODS AND RESULTS: During open heart surgery, we recorded activation from both atria simultaneously using 512 electrodes in 7 patients with persistent and LSP AF. The phase analysis was compared to manual measurements during 4 s of data. For the accuracy of activation sequence maps, a successful recording site was defined as having ≤4 mismatched activation times during the 4 s. In all AF episodes, the accuracy of the phase analysis was only 82% of the total number of activation times due to either activation time differences (14.7%), under-sensing (2.7%), or over-sensing (0.6%). Only 67.9% of the total recording sites met the requirement of a successful recording site by phase analysis. In unsuccessful recording sites, AEG characteristics were relatively irregular cycle length (CL), complex AEG, and double potential AEG. CONCLUSION: The phase analysis was less accurate in recording sites with a relatively irregular CL, complex AEG, or double potential AEG. As a result, phase analysis may lead to the misinterpretation of atrial activation patterns during AF. A visual review of the original AEG is needed to confirm the detected AF sources of phase analysis before performing targeted ablation.

Anticoagulation in new-onset postoperative atrial fibrillation: An analysis from the Society of Thoracic Surgeons Adult Cardiac Surgery Database.

Background: New-onset postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and is associated with increased long-term stroke and mortality. Anticoagulation has been suggested as a potential therapy, but data on safety and efficacy are scant. Objectives: To determine the association between anticoagulation for POAF and long-term outcomes. Methods: Adult patients with POAF after isolated coronary artery bypass surgery (CABG) were identified through the Society of Thoracic Surgeons Adult Cardiac Surgery Database and linked to the Medicare Database. Propensity-matched analyses were performed for all-cause mortality, stroke, myocardial infarction, and major bleeding for patients discharged with or without anticoagulation. Interaction between anticoagulation and CHA2DS2-VASc score was also assessed. Results: Of 38,936 patients, 9861 (25%) were discharged on oral anticoagulation. After propensity score matching, discharge anticoagulation was associated with increased mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.06-1.26). There was no difference in ischemic stroke between groups (HR 0.97, 95% CI 0.82-1.15), but there was significantly higher bleeding (HR 1.60, 95% CI 1.38-1.85) among those discharged on anticoagulation. Myocardial infarction was lower in the first 30 days for those discharged on anticoagulation, but this effect decreased over time. The incidence of all complications was higher for patients with CHA2DS2-VASc scores ≥5 compared to patients with scores of 2-4. Anticoagulation did not appear to benefit either subgroup. Conclusion: Anticoagulation is associated with increased mortality after new-onset POAF following CABG. There was no reduction in ischemic stroke among those discharged on anticoagulation regardless of CHA2DS2-VASc score.

Reliable pace termination of postoperative atrial fibrillation in the canine sterile pericarditis model: Implications for atypical atrial flutter.

BACKGROUND: We have identified a reentrant circuit in the pulmonary vein region, which drives the atria, producing fibrillatory conduction, as one mechanism of postoperative atrial fibrillation (POAF) in the canine sterile pericarditis model. OBJECTIVE: In this model, we tested the hypothesis that overdrive pacing from a site at or near such a reentrant circuit would interrupt it and thereby terminate POAF. METHODS: We studied 11 sterile pericarditis dogs on postoperative days 1-4. Atrial electrograms (AEGs) were recorded during POAF, overdrive pacing, and pace termination from 3 sites simultaneously: Bachmann's bundle, posterior left atrium, and right atrial appendage. When recorded AEGs demonstrated regular activation, pace termination was attempted at that site by delivering a drive train starting with 4 consecutive beats at a cycle length (CL) of 2-5 ms shorter than that of the intrinsic CL. RESULTS: Sixteen episodes of sustained POAF (>5 minutes) diagnosed by electrocardiogram were induced. During all episodes of POAF, AEGs recorded from the left atrium exhibited regular activation, ie, constant AEG morphology and CL. When capture of the reentrant circuit by overdrive pacing occurred (mean 13 ± 5, range 5-23 beats), all 16 POAF episodes were successfully terminated. In all termination episodes, at the end of pacing but prior to the return of sinus rhythm, there was disorganized atrial activation in the previously organized sites (mean 2 seconds, range 0.1-8 seconds). However, these beats did not sustain POAF in the absence of a reentrant circuit ("driver"). CONCLUSION: Overdrive pacing from a site demonstrating regular activation during sustained POAF terminated the POAF by interrupting the reentrant circuit.

Three-year outcomes of the postapproval study of the AtriCure Bipolar Radiofrequency Ablation of Permanent Atrial Fibrillation Trial.

OBJECTIVES: The Cox Maze IV operation is commonly performed concomitant with other cardiac operations and effectively reduces the burden of atrial fibrillation. Prospective randomized trials have reported outcomes early and at 12 months, but only single-center late durability results are available. As part of the postapproval process for a bipolar radiofrequency ablation system, we sought to determine early and midterm outcomes of patients undergoing the Cox Maze IV operation. METHODS: A prospective, multicenter, single-arm study of 363 patients (mean age, 70 years, 82% valve surgery) with nonparoxysmal atrial fibrillation (mean duration, 60 months, 94% Congestive heart failure, Hypertension, Age ≥ 75, Diabetes, Stroke, VAScular disease, Age 65-74, Sex category ≥2) undergoing concomitant Maze IV atrial fibrillation ablation at 40 sites with 70 surgeons was performed between June 2010 and October 2014. Compliance with the study lesion set was 94.5%, and 99% had left atrial appendage closure. Freedom from atrial fibrillation was determined by extended monitoring, with a 48-hour Holter monitor minimum. RESULTS: There were no device-related complications. Freedom from atrial fibrillation off antiarrhythmic medications at 1, 2, and 3 years was 66%, 65%, and 64%, respectively, and including those using antiarrhythmics was 80%, 78%, and 76%, respectively. Warfarin was used in 49%, 44%, and 40%, respectively. CONCLUSIONS: In patients with nonparoxysmal atrial fibrillation, compliance with the protocol was high, and freedom from atrial fibrillation off antiarrhythmics was high and sustained to 3 years. The safety and effectiveness of the system and Cox Maze IV procedure support the Class I guideline recommendation for concomitant atrial fibrillation ablation in patients undergoing cardiac surgery.

Paradigm shifts in electrophysiological mechanisms of atrial fibrillation.

Determining the sequence of activation is a major source of information for understanding the electrophysiological mechanism(s) of atrial fibrillation (AF). However, the complex morphology of the electrograms hampers their analysis, and has stimulated generations of electrophysiologists to develop a large variety of technologies for recording, pre-processing, and analysis of fibrillation electrograms. This variability of approaches is mirrored by a large variability in the interpretation of fibrillation electrograms and, thereby, opinions regarding the basic electrophysiological mechanism(s) of AF vary widely. Multiple wavelets, different types of re-entry including rotors, double layers, multiple focal activation patterns all have been advocated, and a comprehensive and commonly accepted paradigm for the fundamental mechanisms of AF is still lacking. Here, we summarize the Maastricht perspective and Cleveland perspective regarding AF mechanism(s). We also describe some of the key observations in mapping of AF reported over the past decades, and how they changed over the years, often as results of new techniques introduced in the experimental field of AF research.

New Insights Into Understanding Rotor Versus Focal Activation in Patients With Persistent Atrial Fibrillation.

OBJECTIVES: This study was to test the hypotheses that: 1) when using phase analysis, repetitive Wannabe re-entry produces a phase singularity point (i.e., a rotor); and 2) the location of the stable rotor is close to the focal source. BACKGROUND: Recent contact mapping studies in patients with persistent atrial fibrillation (AF) demonstrated that phase analysis produced a different mechanistic result than classical activation sequence analysis. Our studies in patients with persistent AF showed that focal sources sometimes produced repetitive Wannabe re-entry, that is, incomplete re-entry. METHODS: During open heart surgery, we recorded activation from both atria simultaneously using 510 to 512 electrodes in 12 patients with persistent AF. We performed activation sequence mapping and phase analyses on 4 s of mapped data. For each detected stable rotor (>2 full rotations [720°] recurring at the same site), the corresponding activation patterns were examined from the activation sequence maps. RESULTS: During AF, phase singularity points (rotors) were identified in both atria in all patients. However, stable phase singularity points were only present in 6 of 12 patients. The range of stable phase singularity points per patient was 0 to 6 (total 14). Stable phase singularity points were produced due to repetitive Wannabe re-entry generated from a focal source or by passive activation. A conduction block sometimes created a stable phase singularity point (n = 2). The average distance between a focal source and a stable rotor was 0.9 ± 0.3 cm. CONCLUSIONS: Repetitive Wannabe re-entry generated stable rotors adjacent to a focal source. No true re-entry occurred.

Women and atrial fibrillation.

Atrial fibrillation (AF) remains a growing problem in the United States and worldwide, imposing a high individual and health system burden, including increased resource consumption due to repeated hospitalizations, stroke, dementia, heart failure, and death. This comprehensive review summarizes the most recent data on sex-related differences in risks associated with AF. Women with AF have increased risk of stroke and death compared to men, and possible reasons for this disparity are explored. Women also continue to have worse symptoms and quality of life, and poorer outcomes with stroke prevention, as well as with rate and rhythm control management strategies. Many current rhythm control treatment strategies for AF, including cardioversion and ablation, are used less frequently in women as compared to men, whereas women are more likely to be treated with rate control strategies or antiarrhythmic drugs. Sex differences should be considered in treating women with AF to improve outcomes and women and men should be offered the same interventions for AF. We need to improve the evidence base to understand if variation in utilization of rate and rhythm control management between men and women represents health inequities or appropriate clinical judgement.

Is competitive atrial pacing a possible trigger for atrial fibrillation? Observations from the RATE registry.

BACKGROUND: A high incidence of asymptomatic atrial tachycardia and atrial fibrillation (AT/AF) has been recognized in patients with cardiac implantable devices (CIED). The clinical significance of these AT/AF episodes remains unclear. Some "device-detected AT/AF" was previously shown to be triggered by competitive atrial pacing (CAP). OBJECTIVE: To investigate and characterize a potential association between CAP and AT/AF in the largest series of observations to date. METHODS: RATE, a multicenter registry, included 5379 patients with CIEDs followed for approximately 2 years. Electrograms (EGMs) from 1352 patients with AT/AF, CAP, or both were analyzed by experienced adjudicators to assess a causal relationship between AT/AF and CAP onset, duration, and morphology. RESULTS: In 225 patients, 1394 episodes of both AT/AF and CAP were present in the same tracing. CAP and AT/AF were strongly associated (P ≤ .02). AT/AF occurred during the course of the study in 71% of patients with CAP. In 62% of the episodes, expert adjudication concluded that CAP triggered AT/AF. The duration and morphology of triggered and spontaneous AT/AF episodes differed. Spontaneous AT/AF episodes were associated with constant EGM morphology, and were either long or extremely short. CAP-triggered AT/AF more often had variable and shorter cycle length EGMs. The incidence of short AT/AF events was higher among triggered episodes (25% vs 12.8%, P < .002). CONCLUSION: Device-triggered AT/AF due to CAP is likely more common than previously recognized. This AT/AF entity differs from spontaneous AT/AF in duration and morphology. Clinical implications of spontaneous and device-triggered AT/AF may be different.

Attitudes toward anticoagulation for postoperative atrial fibrillation: A nationwide survey of VA providers.

INTRODUCTION: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. Though often felt to be self-limited, this complication has been associated with increases in both short and long-term stroke and mortality. Several studies have also shown a high rate of AF recurrence. Optimal treatment strategy is not yet defined, and the role of anticoagulation (AC) is unclear. Our objective was to determine provider attitudes toward management of this common complication. METHODS: A survey consisting of 15 multiple choice questions was distributed to providers at Veterans Healthcare Administration hospitals nationwide. RESULTS: The majority of respondents were cardiologists. Practices varied drastically with respect to AC use for patients with POAF who were discharged in normal sinus rhythm. Less variability existed for patients discharged in AF. There was no clear consensus regarding other factors to consider when deciding on AC therapy, including length of episode, or risk factors for stroke such as CHA2 DS2 -VASc score. There was also no consensus on duration of therapy or need for post discharge cardiac monitoring. CONCLUSION: Our data indicate a wide variability in the management of POAF. This reflects conflicting recommendations in the guidelines, as well as a paucity of prospective treatment trials in this field. Nevertheless, a growing evidence base suggests that this complication carries potentially serious long-term morbidity and mortality, and better evidence for its management is needed.

Reconsidering the multiple wavelet hypothesis of atrial fibrillation.

BACKGROUND: Moe and Abildskov proposed the multiple wavelet hypothesis of atrial fibrillation (AF) on the basis of observations in the canine vagal nerve stimulation (VNS) AF model. Data from mapping studies in an in vitro canine AF model by Allessie et al (Allessie MA, Lammers WJEP, Bonke FIM, Hollen SJ. Experimental evaluation of Moe's multiple wavelet hypothesis of atrial fibrillation. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology and Arrhythmias. Orlando, FL: Grune & Stratton; 1985:265-275.) were used to evaluate the Moe/Abildskov hypothesis, which revealed that a critical number of wavelets sustained AF. OBJECTIVE: The purpose of this study was to reassess VNS mapping data using the same methods used by Allessie to evaluate Moe's multiple wavelet hypothesis. METHODS: Using the canine VNS AF model in 6 dogs, 510 unipolar atrial electrograms were recorded simultaneously from both atria. Activation sequence maps were produced from sustained AF during VNS in each dog. Per Allessie, consecutive 10 ms activation windows were analyzed over a period of 300 ms. Repetitive activation analysis was applied to Moe's canine VNS AF model. RESULTS: The number of wavefronts in each AF episode was 0-8 in Allessie's studies measured by sequential atrial mapping and 0-10 in our biatrial simultaneous mapping studies. In both studies, an electrically silent period was observed in each atrium and was reactivated by wavefronts emanating from focal sources. Allessie postulated that an electrically silent atrium was reactivated by a wavefront propagating from the other atrium. However, in our biatrial simultaneous mapping studies, each electrically silent atrium was reactivated by a distinct focal source. CONCLUSION: Data from both studies showed a similar number of wavefronts, similar AF activation patterns, and periods of electrical atrial silence reactivated by focal sources. Also, in our studies, independent focal sources initiated wavefronts reactivating the atria, thereby explaining the mechanism maintaining AF.

Contemporary Anticoagulation Practices for Postoperative Atrial Fibrillation: A Single Center Experience.

AIMS: Postoperative atrial fibrillation (POAF) is a frequent in-hospital complication after cardiac surgery. Surprisingly, despite its prevalence, management of this condition has not been well studied. One promising approach that has been evaluated in a limited number of studies is use of anticoagulation. However, the trends and patterns of real-world use of anticoagulation in POAF patients has not been systemically investigated. In this study, we aimed to determine real-world patterns of anticoagulation use for patients with POAF. METHODS: We identified 200 patients undergoing coronary artery bypass (CABG) or cardiac valve surgery at University Hospitals Cleveland Medical Center over a 2 year period beginning January 2016 with new onset POAF. We reviewed charts to verify candidacy for inclusion in the study and to extract data on anticoagulation use, adverse outcomes, and CHA2DS2-VASc scores. RESULTS: Anticoagulation use was low after CABG, but high after bioprosthetic valve surgery. The most common anticoagulant used was warfarin. Anticoagulation use was not correlated with CHA2DS2-VASc score or cardioversion. Stroke and mortality were higher among patients not receiving anticoagulation, however, confirmation of this finding in larger randomized studies is warranted. CONCLUSIONS: Anticoagulation use is low after CABG and this practice does not appear to be affected by CHA2DS2VASc score or cardioversion. This differs with previously reported provider attitudes towards management of this condition. Stroke and mortality appear to be elevated for patients not receiving anticoagulation but further investigation is required to confirm this observation.

Effect of Lidocaine Injection of Ganglionated Plexi in a Canine Model and Patients With Persistent and Long-Standing Persistent Atrial Fibrillation.

Background This study assessed the effect of blockading neural transmission in the ganglionated plexi by injecting lidocaine into fat pads in the vagal nerve stimulation canine model and patients with persistent atrial fibrillation ( AF ). Methods and Results An efficacy test of lidocaine injection was performed in 7 canines. During vagal nerve stimulation, AF was sustained for >5 minutes. The lidocaine was injected into ganglionated plexi during sinus rhythm and reinduction of AF was attempted. Six patients with persistent AF were studied at open heart surgery. Lidocaine was injected into ganglionated plexi. Atrial electrograms were recorded from 96 epicardial electrodes covering Bachmann's bundle and atrial appendages. In the canine vagal nerve stimulation AF model, AF was not inducible in 4 of 7 after lidocaine injection. In patients with persistent AF , during baseline AF , there was a left atrium ( LA )-to-right atrium ( RA ) frequency gradient ( LA , mean cycle length [ CL ] 175±17 ms; RA , mean CL 192±17 ms; P<0.01). After lidocaine injection, AF persisted in all patients, and the LA -to- RA frequency gradient disappeared ( LA , mean CL 186±13 ms; RA , mean CL 199±23 ms; P=0.08). Comparison of mean CL s before and after lidocaine demonstrated prolongation of LA CL s ( P<0.05) with no effect on RA CL s. Conclusions In the canine vagal nerve stimulation AF model, lidocaine injection decreased inducibility of AF . In patients with persistent AF , atrial electrograms from the LA had shorter CL s than RA , indicating an LA -to- RA frequency gradient. Lidocaine injection significantly prolonged only LA CL s, explaining disappearance of the LA -to- RA frequency gradient. The mechanism of localized atrial electrogram CL prolongation in patients with persistent AF is uncertain.

Revisiting an Underrecognized Strategy for Rhythm Management: Hybrid Therapy for Patients who Convert from Atrial Fibrillation to Flutter on Antiarrhythmic Drugs.

Atrial fibrillation (AF) is often treated with antiarrhythmic drugs (AADs) or catheter ablation. In a unique subset of patients, AF can convert to atrial flutter (AFL) after the initiation of an AAD. It has previously been shown that, in this subset of patients, cavotricuspid isthmus (CTI) ablation followed by the continuation of the AAD regimen has an unusually high rate of successfully maintaining sinus rhythm. This is an underrecognized approach toward rhythm management in such patients. However, the reason(s) for such a high degree of efficacy with this hybrid therapeutic approach are unclear. We suggest that conversion from AF to AFL selects for a group of patients in whom AF is particularly responsive to the effects of the AAD. Since CTI ablation is essentially curative of AFL, the combination of both techniques results in a high efficacy of sinus rhythm maintenance. Further investigation is required to confirm these hypotheses.

Incidence and Clinical Significance of New-Onset Device-Detected Atrial Tachyarrhythmia: A Meta-Analysis.

BACKGROUND: Despite the clear association between atrial fibrillation and risk for thromboembolic events (TEs), the clinical significance of new-onset device-detected atrial tachyarrhythmia (DDAT) and TE remains disputed. We aimed to determine the risk of TE in patients with new-onset DDAT. METHODS AND RESULTS: The OVID Medline, Cochrane, and Scopus databases (inception to November 2016) were searched. Randomized controlled trials, prospective, or retrospective studies of pacemaker or defibrillator patients reporting incidence of DDAT were selected. Summary statistics were used for analysis. Of 4893 reports identified, 28 studies following 24 984 patients were included: average age 69.9 years, 34.7% women, mean study duration 21.8±18.6 months. New-onset DDAT was observed in 23% of patients. Among 9 studies (n=8181) reporting TE, the absolute incidence was 2.1%. TE risk was significantly greater among patients with new-onset DDAT (relative risk [RR], 2.88; 95% CI, 1.79-4.64; P<0.001). TE risk was correlated with DDAT duration, with an increased risk associated with DDAT ≥5 minutes (RR, 3.86; 95% CI, 2.04-7.30; P<0.001) compared with <1 minute (RR, 1.77; 95% CI, 1.15-2.74; P=0.01). Notably, the risk of TE was also increased in patients with adjudicated atrial electrograms (RR, 3.60; 95% CI, 2.06-6.30; P<0.001) compared with nonadjudicated electrograms (RR, 2.05; 95% CI, 1.06-3.97; P=0.03), even when lower mean thresholds for detection were used. CONCLUSIONS: New-onset DDAT is common, affecting close to one quarter of all patients with implanted pacemakers or defibrillators. Adjudication of atrial electrograms further identifies at-risk patients, even when relatively short detection thresholds are used.

Implantable Cardioverter-Defibrillators With Versus Without Resynchronization Therapy in Patients With a QRS Duration >180 ms.

BACKGROUND: More than 20% of Medicare beneficiaries receiving cardiac resynchronization therapy defibrillators (CRT-D) have a very wide (≥180 ms) QRS complex duration (QRSD). Outcomes of CRT-D in these patients are not well-established because they have been underrepresented in clinical trials. OBJECTIVES: This study examined outcomes in patients with CRT-D in a very wide QRSD with left bundle branch block (LBBB) versus those without LBBB. METHODS: Medicare patients from the Implantable Cardioverter Defibrillator Registry (January 1, 2005, through April 30, 2006) with a CRT-D and confirmed Class I or IIa indications for CRT-D were matched to implantable cardioverter-defibrillator (ICD) patients without CRT despite having Class I or IIa indications for CRT. Mortality and heart failure hospitalizations longer than 4 years with CRT-D versus standard ICDs based on a QRSD and morphology were analyzed. RESULTS: We analyzed 24,960 patients. Among those with LBBB, patients with a QRSD ≥180 ms had a greater adjusted survival benefit with CRT-D versus standard ICD (hazard ration [HR] for death: 0.65; 95% confidence interval [CI]: 0.59 to 0.72) compared with those having a QRSD 120 to 149 ms (HR: 0.85; 95% CI: 0.80 to 0.92) and 150 to 179 ms (HR: 0.87; 95% CI: 0.81 to 0.93). CRT-D versus ICD was associated with an improvement in survival in those with LBBB and a QRSD ≥180 ms (adjusted HR for death: 0.78; 95% CI: 0.68 to 0.91), but not in those with LBBB and a QRSD 150 to 179 ms (adjusted HR for death: 1.06; 95% CI: 0.95 to 1.19). CONCLUSIONS: Improvements in both survival and heart failure hospitalizations with CRT-D were greatest in patients with a QRSD ≥180 ms with or without LBBB, whereas patients with a QRSD 150 to 179 ms without LBBB had no improvement in survival with CRT-D, and those with a QRSD 150 to 179 ms and LBBB had only a modest improvement.