Atrial Fibrillation Cycle Length Prolongation Research Articles

Selective complex fractionated atrial electrogram ablation based on the number-of-fractionation for persistent atrial fibrillation refractory to pulmonary vein isolation.

Previous studies have suggested that the prolonged or highly fractionated electrograms during atrial fibrillation (AF) are closely related to the reentrant driver regions. We hypothesized that exploration and ablation of these critical complex atrial fractionated electrograms (CFAE) may improve the outcome of persistent AF (PeAF) refractory to conventional PVI. A total of 73 PeAF patients with residual inducibility or failed cardioversions of AF after PVI were enrolled and underwent number-of-fractionation mapping (NFM) by counting the number of fractionations in 2.5s at each of the points using the CARTO3 (ICL mode) and EnSite (fractionation map) systems. After NFM, selective CFAE ablation (NFM-CA) targeting the sites of the upper 40% of the counted fraction number (NF40) was performed as an additional procedure for refractory PeAF. We investigated the prognosis of these patients within 24months after the index ablation procedure and the relationship between changes in activation patterns during the ablation procedure and their prognosis. We also performed a propensity score-matched analysis comparing these patients with historical controls (HC) to identify the optimal indications for NFM-CA. The AF/AT free survival rate was 79.1% at 12months and 56.7% at 24months. Patients with AF termination or AF cycle length prolongation > 21ms during the procedure had significantly better AF/AT-free survival rates than those without notable activation changes (87.7% vs. 69.0%, logrank p = 0.028). After propensity-matched analysis, AF/AT-free survival showed comparable results between the two groups (1year; NFM 72.1% vs. HC 77.1%, logrank p = 0.649). NFM-CA is a versatile and less invasive adjunctive procedure for patients with PVI-refractory PeAF who showed a comparable prognosis to patients with PVI-compliant PeAF. In particular, remarkable activation changes during the procedure (AFCL prolongation > 21ms or acute termination) suggest a favorable prognosis.

Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction.

AimsPharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145.Methods and resultsEight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred.ConclusionAP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.

Inhibition of Small-Conductance Calcium-Activated Potassium Current (I K,Ca) Leads to Differential Atrial Electrophysiological Effects in a Horse Model of Persistent Atrial Fibrillation.

BackgroundSmall-conductance Ca2+-activated K+ (KCa2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the KCa2 current—and thereby the efficacy of small-conductance Ca2+-activated K+ current (IK,Ca) inhibition—might be negatively related to AF duration and the extent of AF-induced remodeling.Experimental Approach and MethodsTo address the hypothesis of the efficacy of IK,Ca inhibition being dependent on AF duration, the anti-arrhythmic properties of the IK,Ca inhibitor NS8593 (5 mg/kg) and its influence on atrial conduction were studied using epicardial high-density contact mapping in horses with persistent AF. Eleven Standardbred mares with tachypacing-induced persistent AF (42 ± 5 days of AF) were studied in an open-chest experiment. Unipolar AF electrograms were recorded and isochronal high-density maps analyzed to allow for the reconstruction of wave patterns and changes in electrophysiological parameters, such as atrial conduction velocity and AF cycle length. Atrial anti-arrhythmic properties and adverse effects of NS8593 on ventricular electrophysiology were evaluated by continuous surface ECG monitoring.ResultsIK,Ca inhibition by NS8593 administered intravenously had divergent effects on right and left AF complexity and propagation properties in this equine model of persistent AF. Despite global prolongation of AF cycle length, a slowing of conduction in the right atrium led to increased anisotropy and electrical dissociation, thus increasing AF complexity. In contrast, there was no significant change in AF complexity in the LA, and cardioversion of AF was not achieved.ConclusionsIntra-atrial heterogeneity in response to IK,Ca inhibition by NS8593 was observed. The investigated dose of NS8593 increased the AF cycle length but was not sufficient to induce cardioversion. In terms of propagation properties during AF, IK,Ca inhibition by NS8593 led to divergent effects in the right and left atrium. This divergent behavior may have impeded the cardioversion success.

Mechanisms by Which Ranolazine Terminates Paroxysmal but Not Persistent Atrial Fibrillation.

Ranolazine inhibits Na+ current (INa), but whether it can convert atrial fibrillation (AF) to sinus rhythm remains unclear. We investigated antiarrhythmic mechanisms of ranolazine in sheep models of paroxysmal (PxAF) and persistent AF (PsAF). PxAF was maintained during acute stretch (N=8), and PsAF was induced by long-term atrial tachypacing (N=9). Isolated, Langendorff-perfused sheep hearts were optically mapped. In PxAF ranolazine (10 μmol/L) reduced dominant frequency from 8.3±0.4 to 6.2±0.5 Hz (P<0.01) before converting to sinus rhythm, decreased singularity point density from 0.070±0.007 to 0.039±0.005 cm-2 s-1 (P<0.001) in left atrial epicardium (LAepi), and prolonged AF cycle length (AFCL); rotor duration, tip trajectory, and variance of AFCL were unaltered. In PsAF, ranolazine reduced dominant frequency (8.3±0.5 to 6.5±0.4 Hz; P<0.01), prolonged AFCL, increased the variance of AFCL, had no effect on singularity point density (0.048±0.011 to 0.042±0.016 cm-2 s-1; P=ns) and failed to convert AF to sinus rhythm. Doubling the ranolazine concentration (20 μmol/L) or supplementing with dofetilide (1 μmol/L) failed to convert PsAF to sinus rhythm. In computer simulations of rotors, reducing INa decreased dominant frequency, increased tip meandering and produced vortex shedding on wave interaction with unexcitable regions. PxAF and PsAF respond differently to ranolazine. Cardioversion in the former can be attributed partly to decreased dominant frequency and singularity point density, and prolongation of AFCL. In the latter, increased dispersion of AFCL and likely vortex shedding contributes to rotor formation, compensating for any rotor loss, and may underlie the inefficacy of ranolazine to terminate PsAF.

Impact of acute atrial fibrillation termination and prolongation of atrial fibrillation cycle length on the outcome of ablation of persistent atrial fibrillation: A substudy of the STAR AF II trial

Controversy exists about the impact of acute atrial fibrillation (AF) termination and prolongation of atrial fibrillation cycle length (AFCL) during ablation on long-term procedural outcome. The purpose of this study was to analyze the influence of AF termination and AFCL prolongation on freedom from AF in patients from the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II) trial. Acute changes in AFCL and AF termination were collected during the index procedure of the STAR AF II trial and compared to recurrence of AF at 18 months. Recurrence was assessed by ECG, Holter (3, 6, 9, 12, 18 months), and weekly transtelephonic ECG monitoring for 18 months. AF terminated in 8% of the pulmonary vein isolation (PVI) arm, 45% in the PVI+complex electrogram arm, and 22% of the PVI+linear ablation arm (P <.001), but freedom from AF did not differ among the 3 groups (P = .15). Freedom from AF was significantly higher in patients who presented to the laboratory in sinus rhythm (SR) compared to those without AF termination (63% vs 44%, P = .007). Patients with AF termination had an intermediate outcome (53%) that was not significantly different from those in SR (P = .84) or those who did not terminate (P = .08). AF termination was a univariable predictor of success (P = .007), but by multivariable analysis, presence of early SR was the strongest predictor of success (hazard ratio 0.67, P = .004). Prolongation of AFCL was not predictive of 18-month freedom from AF. Acute AF termination and prolongation in AFCL did not consistently predict 18-month freedom from AF. Presence of SR before or early during the ablation was the strongest predictor of better outcome.

Catheter Ablation for Persistent Atrial Fibrillation

A new era of atrial fibrillation (AF) treatment began in 1997–1998 with the discovery that triggers within the pulmonary veins initiate AF and reports that elimination of these triggers is successful in treating AF in its paroxysmal form.1–3 However, in patients with persistent AF, the success rate of exclusive pulmonary vein isolation is substantially lower.4,5 To improve the outcome of persistent AF ablation, different ablation strategies have been explored, but to date the optimal strategy has not been defined. Although some groups argue that limited ablation, including pulmonary vein isolation and, if present, ablation of nonpulmonary vein triggers, is sufficient for persistent AF ablation, other groups, including ours, favor more extensive, substrate-based ablation in addition to pulmonary vein isolation. In this review, we will discuss the rationale for a substrate-based ablation strategy to treat persistent AF and show why elimination of triggers is not sufficient in most patients with persistent AF. Response by Roten et al on p 1232 In a simple model, an electric impulse in AF can form because of abnormalities in impulse generation (triggers) or can result from abnormal impulse propagation (reentry). By a strict definition, a trigger is a focal source of new impulse generation. The mechanism by which a new impulse can form is either abnormal automaticity or triggered activity. Trigger-ablation protocols target these sources of new impulse generation. Abnormal impulse propagation, on the other hand, depends on altered substrate properties causing nonuniform or slowed conduction. This in turn causes multiple forms of wave reentry thought to be responsible for AF perpetuation: random reentry (multiple wavelets), macro- and microreentry, or functional reentry (rotors). Substrate-based ablation strategies aim to abate abnormal impulse propagation and interrupt any form of atrial reentry. Triggers of paroxysmal AF are mainly located in the pulmonary …

Disparate Evolution of Right and Left Atrial Rate During Ablation of Long-Lasting Persistent Atrial Fibrillation

The purpose of this study was to assess whether additional ablation in the right atrium (RA) improves termination rate in long-lasting persistent atrial fibrillation (PsAF). Prolongation of atrial fibrillation (AF) cycle length (CL) measured from the left atrial appendage predicts favorable outcome during catheter ablation of PsAF. However, in some patients, despite prolongation of AF CL in the left atrium (LA) with ablation, AF persists. We hypothesized that this persistence is due to RA drivers, and that these patients may benefit from RA ablation. In all, 148 consecutive patients undergoing catheter ablation of PsAF (duration 25 +/- 32 months) were studied. AF CL was monitored in both atria during stepwise ablation commencing in the LA. Ablation was performed in the RA when all LA sources in AF had been ablated and an RA-LA gradient existed. The procedural end point was AF termination. Two distinct patterns of AF CL change emerged during LA ablation. In 104 patients (70%), there was parallel increase of AF CL in LA and RA culminating in AF termination (baseline: LA 153 ms [range 140 to 170 ms], RA 155 ms [range 143 to 171 ms]; after ablation: LA 181 ms [range 170 to 200 ms], RA 186 ms [range 175 to 202 ms]). In 24 patients (19%), RA AF CL did not prolong, creating a right-to-left frequency gradient (baseline: LA 142 ms [range 143 to 153 ms], RA 145 ms [range 139 to 162 ms]; after ablation: LA 177 ms [range 165 to 185 ms], RA 152 ms [range 147 to 175 ms]). These patients had a longer AF history (23 months vs. 12 months, p = 0.001), and larger RA diameter (42 mm vs. 39 mm, p = 0.005), and RA ablation terminated AF in 55%. In the remaining 20 patients, biatrial ablation failed to terminate AF. A divergent pattern of AF CL prolongation after LA ablation resulted in a right-to-left gradient, demonstrating that the right atrium is driving AF in approximately 20% of PsAF.

Centrifugal Gradients of Rate and Organization in Human Atrial Fibrillation

Animal studies show that atrial fibrillation (AF) may emanate from sites of high rate and regularity, with fibrillatory conduction to adjacent areas. We used simultaneous mapping to find evidence for potential drivers in human AF defined as sites with higher rate and regularity than surrounding tissue. In 24 patients (age 61+/-10 years; 12 persistent), we recorded AF simultaneously from 32 left atrial bipolar basket electrodes in addition to pulmonary veins (PV), coronary sinus, and right atrial electrodes. We measured AF cycle length (CL) by Fourier transform and electrogram regularity at each electrode, referenced to patient-specific atrial anatomy. We analyzed 10,298 electrode-periods. Evidence for potential AF drivers was found in 11 patients (five persistent). In persistent AF, these sites lay at the coronary sinus and left atrial roof but not PVs, while in paroxysmal AF six of nine sites lay at PVs (P<0.05). During ablation, a subset of patients experienced AF CL prolongation or termination with a focal lesion; in each case this lesion mapped to potential driver sites on blinded analysis. Conversely, sequential mapping failed to reveal these sites, possibly due to fluctuations in dominant frequency at driver locations in the context of migratory AF. Simultaneous multisite recordings in human AF reveal evidence for drivers that lie near PVs in paroxysmal but not persistent AF, and were sites where ablation slowed or terminated AF in a subset of patients. The future work should determine if real-time ablation of AF-maintaining regions defined in this fashion eliminates AF.

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

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. 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). 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. 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). 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.

Transthoracic Tissue Doppler Imaging of the Atria: A Novel Method to Determine the Atrial Fibrillation Cycle Length

The atrial fibrillation cycle length (AFCL) is a critical parameter for the perpetuation and termination of AF. In the present study, we evaluated a new method to measure the AFCL based on transthoracic tissue Doppler imaging (TDI) of the right atrium (RA) and left atrium (LA). Twenty patients with AF (6 acute AF, 14 persistent or permanent AF) were studied. A quadripolar catheter was positioned at RA or LA to measure AFCL (AFCL(EGM), gold standard). Transthoracic echocardiography (apical 4-chamber view) was used to perform pulsed wave TDI at the free wall of RA or LA. AFCL(TDI) was defined as the time interval between two consecutive positive to negative crossings of the baseline of the atrial time velocity curves. AFCL(EGM) and AFCL(TDI) were measured at baseline and during a 10-minute infusion of flecainide (1.5 mg/kg). Measurement of AFCL(TDI) was feasible in all but one patient. At baseline, AFCL(EGM) was 170 +/- 22 ms, AFCL(TDI) 172 +/- 22 ms (difference 2 +/- 5 ms). AFCL(TDI) correlated significantly with AFCL(EGM) (R = 0.91, P < 0.0001). Bland-Altman analysis showed a bias of -2 ms with a 95% limit of agreement between -26 ms and +22 ms. During flecainide, the AFCL(TDI) method yielded an AFCL prolongation from 176 +/- 23 ms at baseline to 279 +/- 68 ms (P < 0.01) after 10 minutes of infusion (57 +/- 26%). (1) Tissue Doppler imaging of the atria during transthoracic echocardiography can be used to reliably determine the AFCL during both acute and persistent or permanent AF. (2) Continuous measurement of AFCL with TDI can be used to monitor the effect of antiarrhythmic drugs on atrial rate during AF. (3) This novel method is attractive because of the ease of acquiring the data and its noninvasive character.

Catheter Ablation of Long‐Lasting Persistent Atrial Fibrillation: Critical Structures for Termination

The relative contributions of different atrial regions to the maintenance of persistent atrial fibrillation (AF) are not known. Sixty patients (53 +/- 9 years) undergoing catheter ablation of persistent AF (17 +/- 27 months) were studied. Ablation was performed in a randomized sequence at different left atrial (LA) regions and comprised isolation of the pulmonary veins (PV), isolation of other thoracic veins, and atrial tissue ablation targeting all regions with rapid or heterogeneous activation or guided by activation mapping. Finally, linear ablation at the roof and mitral isthmus was performed if sinus rhythm was not restored after addressing the above-mentioned areas. The impact of ablation was evaluated by the effect on the fibrillatory cycle length in the coronary sinus and appendages at each step. Activation mapping and entrainment maneuvers were used to define the mechanisms and locations of intermediate focal or macroreentrant atrial tachycardias. AF terminated in 52 patients (87%), directly to sinus rhythm in 7 or via the ablation of 1-6 intermediate atrial tachycardias (total 87) in 45 patients. This conversion was preceded by prolongation of fibrillatory cycle length by 39 +/- 9 msec, with the greatest magnitude occurring during ablation at the anterior LA, coronary sinus and PV-LA junction. Thirty-eight atrial tachycardias were focal (originating dominantly from these same sites), while 49 were macroreentrant (involving the mitral or cavotricuspid isthmus or LA roof). Patients without AF termination displayed shorter fibrillatory cycles at baseline: 130 +/- 14 vs 156 +/- 23 msec; P = 0.002. Termination of persistent AF can be achieved in 87% of patients by catheter ablation. Ablation of the structures annexed to the left atrium-the left atrial appendage, coronary sinus, and PVs-have the greatest impact on the prolongation of AF cycle length, the conversion of AF to atrial tachycardia, and the termination of focal atrial tachycardias.

Altered electroanatomic patterns of right ventricle in myotonic dystrophy type 1 patients

Background: Prolongation of the atrial fibrillation cycle length (AFCL) and termination of AF during ablation have been reported. We investigate the significance of regions of maximal dominant frequency (DF) identified by spectral analysis, determining the effect of ablation at these sites located within the pulmonary veins (PV) on the fibrillatory process. Methods: Thirty-two patients undergoing AF ablation during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126 13 points/pt throughout both atria and coronary sinus (CS). At each point, 5s electrograms were obtained to determine the highest amplitude frequency on spectral analysis and construct 3D DF maps. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at PVs with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient 20%) was evaluated by determining the change in AFCL within the CS before and after isolation of each PV, and the termination of AF. Results: PV ablation was associated with an increase in AFCL (174 27 to 184 35ms; p 0.0001). While ablation at a PV harboring a DF site resulted in AFCL prolongation (180 30 to 198 40ms; p 0.0001), ablation at a PV without a DF site did not change the AFCL (169 22 to 170 22ms; p 0.4). Ablation at PVs harboring a DF site resulted in an increase in AFCL ( 5ms) within the CS in 89% with the mean increase in AFCL of 18 21ms (range 0-118ms) compared to 0.9 3.9ms (range -10 to 7ms; p 0.0001) after ablation at PVs without a DF site. The increase in AFCL with PV ablation demonstrated a strong concordance with ablation at a DF site (kappa-coefficient of 0.77). PV ablation resulted in AF termination in 14 pts; 11 at a DF site. In the remaining 3, 2 had frequent cessation of arrhythmia during mapping. Conclusion: High frequency PV activity identified by spectral analysis has an important role in maintaining AF. Ablation at these sites resulted in slowing of the fibrillatory process and termination of paroxysmal AF.

977-73 Observations During Induced Atrial Fibrillation and its Spontaneous Termination in the Sterile Pericarditis Model

Atrial fibrillation (AF) is thought to be due to circulating multiple reentrant wavelets, but it is not known how interatrial activation acts to sustain AF. To test the hypothesis that the exchange of reentrant wave fronts between the right and left atria via the intercaval region, septum, and Bachmann's bundle plays a role in the self-sustaining mechanism of AF, we studied activation of both atria during induced AF and during its spontaneous termination. Three hundred seventy-two unipolar electrograms were recorded simultaneously from an electrode array placed on both atrial free walls by using a multiplexing system during 10 induced AF episodes lasting up to 7 minutes in 5 dogs with sterile pericarditis. Activation maps were analyzed during sustained AF and just before termination of AF for 5 consecutive beats, respectively. The mean number of the lines of functional block (LFB) par beat in each atrium, the mean AF cycle length, and the mean number of wave fronts passing between the atria per beat were compared in during sustained AF and before termination of AF in the same AF episode. Complete reentrant circuits were rarely detected in either atrium during AF. Wave fronts traveling in part around LFBs were observed, and the location and length of the LFBs changed from beat-to-beat. The mean number of LFBs detected in the right atrium did not change during sustained AF compared with AF termination (1.7 ± 0.5 vs. 1.8 ± 0.8, NS). However, the mean numberof LFBs in the left atrium significantly decreased from 1.4 ± 1.2 during sustained AF to 0.4 ± 0.6 before AF termination (p &lt; 0.05). The mean AF cycle length significantly prolonged from 107 ± 19 ms during sustained AF to 151 ± 34 ms before AF termination (p &lt; 0.0001). In the beats before AF termination, wave fronts going from left-to-right significantly decreased (1.4 ± 0.5 during AF to 0.4 ± 0.4 before AF termination, p &lt; 0.05). so that the left atrium was activated by right atrial wave fronts. The presence of LFBs associated with partial reentrant circuits in the left atrium and exchange of wave fronts between the atria play an important role in sustaining AF. Spontaneous termination of AF is preceded by prolongation of AF cycle length, decreasing number of LFBs in the left atrium, and a marked decrease in left-to-right activation wave fronts.