Pulmonary Vein Foci Research Articles

PO-04-081 ISOLATION OF PERSISTENT LEFT SIDED SUPERIOR VENA CAVA USING PULSED FIELD ABLATION

Pulmonary vein foci account for more than 90% of triggers for atrial fibrillation, most commonly treated with complete pulmonary vein isolation. Non–pulmonary vein triggers are the drivers of atrial fibrillation in a subgroup of patients. One such trigger is a persistent left superior vena cava (SVC), which may contain remnant muscular and pacemaker tissue carried over from embryonic life. However, reported complications of radiofrequency ablation of this structure are significant, including vein stenosis, tamponade and phrenic nerve injury. Pulsed field ablation is a promising new technology that may be uniquely suited to avoid such a complications. This case illustrates the first known application of pulsed field ablation of a left sided SVC. N/A The patient is a fifty-two year old male with a history of coronary artery disease and persistent atrial fibrillation refractory to medical therapy including rate and rhythm control strategies. He is status post multiple cardioversions with restoration to normal sinus rhythm for a relatively short period of time. The patient underwent an ablation procedure at which time it was discovered that he had an isolated persistent left sided SVC. Pulmonary vein isolation was performed using a combined radiofrequency and pulsed field ablation lattice tip catheter (Affera inc., Watertown, MA). Accordingly to study protocol, lesions were placed using radiofrequency anteriorly and pulsed field lesions posteriorly in the left atrium around the pulmonary veins resulting in complete isolation. The patient also developed a counterclockwise typical atrial flutter which was ablated. Given the propensity for triggers from the SVC, pulsed field ablation was performed by creating a circumferential lesion set superiorly beyond the left superior pulmonary vein region and inferiorly near the mid coronary sinus below the left inferior pulmonary vein. A linear lesion set connecting these two regions was also performed along the atrial portion of the coronary sinus, with subsequent confirmation of exit block and elimination of all local electrograms. In patients with persistent left SVC, pulsed field ablation is feasible without the risk of phrenic nerve injury or tamponade from excessive contact force. Further studies are necessary to examine whether the complications associated with LSVC isolation can be minimized.

Localized reentry in the superior vena cava giving rise to an atypical right atrial flutter: Insights from an analysis of two cases

The superior vena cava is a known arrhythmogenic structure since it can be a non pulmonary vein focus of atrial fibrillation but also a source of fibrillatory activity that in some cases has been reported to mimick atrial flutter. In this report, we demonstrate that another arrhythmogenic mechanism from this vein, that is localized reentry, can cause a specific pattern of atypical right flutter.

Empirical superior vena cava isolation in patients undergoing redo- catheter ablation procedure after recurrence of atrial fibrillation

Abstract Background/Introduction Extra pulmonary vein (PV) foci may trigger AF recurrence after an initially successful PVI. Superior vena cava (SVC) catheter ablation (CA) may therefore offer a treatment target in order to improve success rates. Purpose The purpose of this study was to evaluate the potential benefit of empirical SVC isolation in addition to PVI in patients undergoing a second CA after index PVI. Methods We retrospectively analyzed consecutive patients scheduled for a second CA because of a recurrence of symptomatic AF. Redo-CA was performed with a 3D electroanatomic mapping system and point-by-point ablation using RF energy in the range between 25 W and 30 W. In case of persistent isolation of all PVs, only SVCI was performed. In case of reconnection of vein(s), a wider antral re-isolation was performed. Redo-PVI (PVI-group) or Redo-PVI plus SVC isolation (SVCI) (PVIplusSVCI-group) were performed at the discretion of the operator. No additional targets were allowed. The endpoint of all procedures was elimination of the PV signals confirmed by a circular mapping catheter at the level of the PV ostium and elimination of all signals in the SVC in case of SVCI. Recurrence of AF during a follow-up of 12 months is presented. Results We analyzed 191 patients (age 61±10 years, 30% female, BMI 27±5 kg/m2, LVEF 56±9%, PLAX 41±7 mm, paroxysmal 61%). Whereas 148 (78%) patients underwent Redo-PVI only, 31 patients (16%) underwent PVI plus SVCI, and in 12 patients (6%) SVCI only was performed. Baseline characteristics did not differ significantly between the two groups. In the PVI-group, 79% were recurrence-free compared to 65% (see Kaplan-Meier curve: log rank p=0.011) in the PVIplusSVCI-group. The RF time of the PVI group focusing on the wide antral re-isolation of vein(s) was significantly higher than for the PVIplusSVCI-group (819±494 s versus 458±444 s; p<0.001). Conclusion Additional empirical SVCI at redo-PVI in patients with symptomatic AF recurrence does not lead to an increase in freedom from AF recurrence. Focusing on an additional “wider antral” re-isolation may be more effective. Kaplan-Meier Survival Curves for Recurre Funding Acknowledgement Type of funding source: None

The Rapid Prediction of Focal Wavefront Origins: Integration With a 3-Dimensional Mapping System.

This study assessed the accuracy of an algorithm that predicts the origin of focal arrhythmias using a limited number of data points. Despite advances in technology, ablations can be time-consuming, and activation mapping continues to have inherent limitations. The authors developed an algorithm that can predict the origin of a focal wavefront using the location and activation timing information in 2 pairs of sampled points. This algorithm was incorporated into an electroanatomic mapping (EAM) system to assess its accuracy in a 3-dimensional clinical environment. EAM data from patients who underwent successful ablation of a focal wavefront using the CARTO3 system were loaded onto an offline version of the software modified to contain the algorithm. Prediction curves were retrospectively generated. Predictive accuracy, defined as the distance between true and predicted origin wavefront origins, was measured. Seventeen wavefronts in as many patients (2 with atrial tachycardia, 3 with orthodromic re-entrant tachycardia, 8 with premature ventricular complex and/or ventricular tachycardia, 4 with focal pulmonary vein isolation breakthroughs) were studied. Thirty-three origin predictions were attempted (1.9 ± 0.4 per patient) using 132 points. Predictions were successfully calculated in 31 of 33 (93.9%) attempts and were accurate to within 5.7 ± 6.9mm. Individual prediction curves were accurate to within 3.0 ± 4.7mm. Focal wavefront origins may be accurately predicted in 3 dimensions using a novel algorithm incorporated into an EAM system.

Role of LVA Ca channels in norepinephrine-induced automatic activity in rat pulmonary vein myocardial sleeve

Ectopic foci in pulmonary veins (PV) are involved in the onset of atrial fibrillation. Norepinephrine (NE) induces in rat PV cardiomyocytes (CM) an automatic activity in saw-tooth pattern (catecholaminergic automatic activity or CAA), consisting of bursts of slow action potentials which depends on Ca (upstroke) and Na (inter burst) channels. We have previously shown the co-existence in rat PVCM, of a fast LVA (FLVA) non selective TTX-sensitive cationic channel and of T-type Ca channels. To evaluate in male Wistar rat PV myocardial sleeve the contribution of these channels to triggering NE-induced ectopic foci. Whole-cell currents were studied at room temperature in enzymatically isolated PVCM. Mechanical activity of PV rings was recorded in an organ bath at 37 °C and CAA was induced by application of 10 μM NE. The FLVA Ca current was increased by the Cav3.x blockers TTA-A2 (10-100 nM, n = 11) and NiCl2 (40 μM, n = 9) whereas a large LVA Ca current, present in 10 out of 80 PVCM, was partially reduced by 100 nM TTA-A2. Study of K currents revealed the presence of an inward rectifying current sensitive to TRAM-34 (1 μM, n = 6), a blocker of the Ca-activated K channel SK4. In PV rings, TTA-A2 (1-5 μM) decreased CAA incidence. Total arrhythmia duration, measured over the last 10 min of a 30 min long drug application, was reduced as well as burst duration and the number of spontaneous twitches within a burst. On the other hand, 40 μM NiCl2 or 1-2 μM TRAM-34 increased total arrhythmia duration by decreasing the interval between bursts (no significant effect on the burst characteristics). Only NiCl2 had a significant negative inotropic effect (∼80% inhibition of L-type calcium current). Our results suggest that Ca influx through Cav3.1 channels contribute to triggering bursts of automatic activity and that Cav3.2 Ca channels, through activation of SK4 channels, are involved in the regulation of the interval between bursts.

Co-existence of a fast tetrodotoxin-sensitive low voltage-activated non selective Na/Ca/K channel and of T-type Ca channels in rat isolated pulmonary vein cardiomyocytes

Ectopic foci in pulmonary veins (PV) are involved in the onset of atrial fibrillation. Norepinephrine (NE) induces an automatic activity occurring in bursts in rat PV cardiomyocytes (CM) which depends on Ca (upstroke) and Na (inter-burst) channels. To characterize low voltage-activated (LVA) Ca currents in rat PVCM susceptible to trigger ectopic foci. Whole-cell ICa (5 mM Ca) was recorded from -100 mV with classical Na- and K-free solutions at room temperature in enzymatically isolated PVCM from male Wistar rats. A fast LVA ICa (FLVA-ICa; −1.5 ± 0.2 pA/pF, n = 45; 26% of peak ICa, max recorded at + 20 mV) was activated between −55 and −20 mV in ∼56% of PVCM and blocked by 10 μM tetrodotoxin (TTX). In that, it was similar to the reported TTX-sensitive Ca current. However, it was markedly increased by addition of NaCl (1 or 3 mM) or KCl (5 or 10 mM). Permeability ratios P’Ca/PNa and P’Ca/PK calculated for bi-ionic conditions were respectively 2.25 ± 0.51 (n = 6) and 1.88 ± 0.25 (n = 14), and not different from a value of 2. NE (10 μM, n = 13) increased FLVA-ICa and negatively shifted its activation threshold, an effect partially reversed by 5 μM Atenolol. It was partially blocked by 5 μM Nifedipine (n = 5) and increased by 300 nM BayK8644 (n = 6), but not blocked by Ranolazine (10 μM, n = 6). NiCl2 (40 μM, n = 9) and TTA-A2 (10 or 100 nM, n = 11) increased FLVA-ICa. Neither Ba nor Sr alone could permeate the FLVA channel or block Ca influx but revealed a large slower activating and inactivating LVA Ca current (SLVA-ICa), present in 10 out of 80 PVCM and absent in LACM. SLVA-ICa was partially blocked by 100 nM TTA-A2. The ionic channel underlying FLVA-ICa is likely a fast voltage-gated non-selective channel permeable to Na/Ca/K with a dihydropyridine binding site. SLVA-ICa might correspond to Ca influx through Cav3.1 channels. The respective role of these channels to triggering ectopic foci in the PV myocardial sleeve remained to be determined.

GW28-e1070 Non–Pulmonary Vein Foci in Paroxysmal Atrial Fibrillation: Prevalence, Mechanisms, Induction and Ablation

Studies have demonstrated that pulmonary vein (PV) is the major source of ectopic foci initiating paroxysmal atrial fibrillation (PAF). Pulmonary vein isolation (PVI) is recognized to be the cornerstone of radiofrequency catheter ablation for drug-refractory PAF. However, with broadening of

Mechanistic Approaches to Detect, Target, and Ablate the Drivers of Atrial Fibrillation.

Ablation strategies to treat atrial fibrillation (AF) have evolved from the initial focal pulmonary vein ablation approach of Haissaguerre et al1 to new technical developments aimed at simplifying the procedure and increasing its safety.2 However, ablation procedures are still associated with unsatisfactory rates of long-term success, particularly in persistent and long-term AF.3 We submit that such disappointing outcomes are the result of the intrinsic limitations of a strategy that has relied mainly on anatomic landmarks during the past 2 decades, and paid scant attention to the underlying mechanisms of the arrhythmia. Recently, approaches aimed at localizing and targeting AF sources based on careful analysis of the fibrillatory patterns often obtained via multiple electrode mapping systems (basket-catheter mapping, body surface mapping, and electrocardiographic imaging [ECGI]) have resulted in an increased specificity of ablation procedures, and long-term freedom from AF.4–7 Such mechanistically based ablation techniques have the potential to enable translational insights from experimental animal models into further improved AF ablation therapy. Indeed, they are a direct result of insights into the dynamic behavior of AF drivers, obtained from experimental optical mapping studies and computer simulations of AF dynamics. The purpose of this article is to briefly review the following: (1) competing theories attempting to explain mechanisms underlying AF maintenance, (2) different methodologies to map electric activity during AF, (3) the most recent mechanistic ablation approaches aimed at targeting AF drivers and their outcomes, and (4) the controversies and near-future directions in the quest to increase the understanding of AF mechanisms and improve ablation outcomes. ### Mechanisms Underlying AF Maintenance #### Historical Perspective: Reentry, Ectopic Foci, Random Wavelets, Complex Fractionated Atrial Electrograms, and Endo-Epicardial Breakthroughs AF mechanisms have a long history of controversy.8 During the first half of the 20th century, 2 theories were prevalent: the concept of reentry around an anatomic obstacle (circus movement reentry),9 and the ectopic focus theory.10 Focus isolation …

Incidence, Risk Factors, Prognosis, and Electrophysiological Mechanisms of Atrial Arrhythmias After Lung Transplantation

ObjectivesThe purpose of this study was to investigate the incidence and timing, risk factors, prognostic significance, and electrophysiological mechanisms of atrial arrhythmia (AA) after lung transplantation. BackgroundAlthough new-onset AA is common after thoracic surgery and is associated with poorer outcomes, prognostic and mechanistic data are sparse in lung transplant populations. MethodsA total of 293 consecutive isolated lung transplant recipients without known AA were reviewed retrospectively. Mean follow-up was 28 ± 17 months. Electrophysiology studies (EPS) were performed in 25 patients with AA. ResultsThe highest incidence of new-onset AA after lung transplantation occurred within 30 days after transplantation (25% of all patients). In multivariable analysis, post-operative AA was associated with double-lung transplantation (odds ratio: 2.79; p = 0.005) and lower mean pulmonary artery pressure (odds ratio: 0.95; p = 0.027). Patients with post-operative AA had longer hospital stays (21 days vs. 12 days; p < 0.001). Post-operative AA was independently associated with late AA (hazard ratio: 13.52; p < 0.001) but not mortality (hazard ratio: 1.55; p = 0.14). On EPS, there were 14 patients with atrial flutter alone and 11 with atrial flutter and fibrillation. Among all EPS patients, 20 (80%) had multiple AA mechanisms, including peritricuspid flutter (48%), perimitral flutter (36%), right atrial incisional re-entry (24%), focal tachycardia from recipient pulmonary vein (PV) antrum (32%), focal PV fibrillation (24%), and left atrial roof flutter (20%). Left atrial mechanisms were present in 80% of EPS patients (20 of 25) and originated from the anastomotic PV antrum. ConclusionsPost-operative AA was independently associated with longer length of stay and late AA but not mortality. Pleomorphic PV antral arrhythmogenesis from native PV antrum is the main cause of AA after lung transplantation.

Adenosine-Provoked Atrial Fibrillation Originating From Non–Pulmonary Vein Foci: The Clinical Significance and Outcome After Catheter Ablation

ObjectivesThe goal of this study was to systematically investigate the incidence and clinical significance of non–pulmonary vein (PV) foci revealed by adenosine/adenosine triphosphate (ATP) testing during atrial fibrillation (AF) ablation. BackgroundATP is reported to provoke AF. MethodsA total of 464 patients with consecutive paroxysmal AF undergoing ATP testing after PV antrum isolation were included. ResultsAF originating from non-PV foci was provoked in 26 (5.6%) total patients during first (n = 20) or repeat (n = 8) ablation procedures. Dormant PV conduction was also revealed by ATP testing in 6 patients. Non-PV foci were located in the superior vena cava (SVC) (i.e., the SVC group) and atria (i.e., the atria group) in 10 and 18 (9 each in the right and left atria) patients, respectively. In the multivariable analysis, being female was the sole independent predictor of ATP-provoked AF originating from non-PV foci (hazard ratio [HR]: 2.52 [95% confidence interval (CI): 1.069 to 5.929]; p = 0.034). After additional ablation targeting non-PV foci, freedom from recurrent AF after the last procedure was similar between the SVC group and patients without ATP-provoked AF but was significantly lower in the atria group than in others (p = 0.0008). Atria group membership (HR: 3.725 [95% CI: 1.692 to 8.199]; p = 0.001) and being female (HR: 1.538 [95% CI: 1.189 to 1.989]; p = 0.001) were significant independent predictors associated with recurrence after the last procedure in the multivariable Cox regression model. ConclusionsATP provoked AF originating from non-PV foci under isoproterenol in 5.6% of patients undergoing paroxysmal AF ablation. ATP testing might be useful for identifying and eliminating AF originating from the SVC. The atria group was associated with a poor outcome after the last procedure despite efforts to eliminate non-PV foci.

Anatomical Characteristics of Pulmonary Veins for the Prediction of Postoperative Recurrence after Radiofrequency Catheter Ablation of Atrial Fibrillation

BackgroundThe relationship between focal pulmonary vein potential and atrial fibrillation (AF) has been confirmed. Pulmonary vein (PV) isolation and circumferential pulmonary vein ablation have been the most commonly used procedures of radiofrequency ablation. However, few studies have investigated the relationship between anatomical characteristics of PV and AF recurrences after radiofrequency ablation.MethodologyFor 267 AF patients treated by radiofrequency catheter ablation, the anatomic structure characteristics of pulmonary veins were assessed by multi-slice spiral computed tomography while the values of left atrial diameter (LAD) were measured with transesophageal ultrasonic cardiogram. After radiofrequency catheter ablation, postoperative recurrence was evaluated during a 10-month term follow-up.Principal FindingsDuring follow-up, postoperative recurrence occurred in 44 patients. The mean diameters of LAD, left superior PV, right superior PV, all left PV, and all superior PV were significantly larger in patients with postoperative recurrence (Recurrence vs. Non-recurrence group; 43.9 ± 6.4 mm vs. 40.7 ± 5.6 mm; 18.4 ± 2.1 mm vs. 17.1 ± 3.1 mm; 18.2 ± 2.8 mm vs. 17.2 mm ± 3.9 mm; 16.4 ± 1.5 mm vs. 15.6 ± 2.5 mm; 18.3 ± 2.1 mm vs. 17.1 ± 3.0 mm; respectively; all P < 0.05). Multivariable survival analysis showed that the type and the course of AF, LAD, and the diameters of all superior PV were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.ConclusionsThe enlargements of all superior PV and LAD, long course of diseases, and persistent AF were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.

Role of Magnetic Resonance Imaging of Atrial Fibrosis in Atrial Fibrillation Ablation.

Atrial fibrillation (AF) likely involves a complex interplay between triggering activity, usually from pulmonary vein foci, and maintenance of the arrhythmia by an arrhythmogenic substrate. Both components of AF, triggers and substrate have been linked to atrial fibrosis and attendant changes in atrial electrophysiology. Recently, there has been a growing use of imaging modalities, particularly cardiac magnetic resonance (CMR), to quantify the burden of atrial fibrosis and scar in patients either undergoing AF ablation, or who have recently had the procedure. How to use the CMR derived data is still an open area of investigation. The aim of this article is to summarise what is known as atrial fibrosis, as assessed by traditional catheter-based techniques and newer imaging approaches, and to report on novel efforts from our group to advance the use of CMR in AF ablation patients.

211: Left atrial flutter occurring after atrial fibrillation ablation: ablation using remote magnetic navigation versus manual technique

Limited data exist on the efficacy and safety of remote magnetic navigation (RMN) ablation of iatrogenic left atrial flutter (LAF) occurring after atrial fibrillation (AF) ablation. LAF ablation procedures (proc) were reviewed. Patients (pts) were divided into 2 groups (gr): RMN gr if proc were performed remotely using the Niobe system (Sterotaxis) and conventional gr (CON) if proc were performed with manually driven catheters. Open-irrigated 3.5 mm-tip catheters were used in all pts. Activation LA maps were realized in all pts using Carto or EnSite). Acute (defined as sinus rhythm- SR- resumption during ablation) and long-term (defined as SR maintenance) proc success, proc duration, fluoroscopy and radiofrequency (RF) times, and the mechanism of arrhythmias were studied. In 46 pts (38 males, 60.8±10.19 y) 57 LAF ablation proc were performed. Age and LA size were similar. Activation maps showed: a unique macro-reentrant circuit 46%, multiples successive macro-reentrant circuits 26%, focal pulmonary vein tachycardia 9%, micro-reentrant circuit 19%. Results are showed in the table. Complications occurred in 3 proc: 1 in the RMN gr (groin hematoma) and 2 in the CON gr (1 transient ischemic attack and 1 cardiac perforation with tamponade). Perimitral flutter that occurred at any stage of the proc was associated with significantly higher rate of acute failure (persistent perimitral flutter at the end of the proc, both gr): 44% vs 12% for other types of flutter, p=0.02. RMN (n= 25) CON (n= 32) p Acute success 80% 78% 0.86 Proc/pt 1.2±0.5 1.2±0.8 0.74 Long-term success (follow-up 12.5±11.3 months) 81% 66% 0.44 Fluoroscopy 748±377 s 1086±772 s 0.05 Proc time 236±68 min 201±72 min 0.06 RF time 1291±880 s 1181±897 s 0.70 As compared to manual proc, RMN guided ablation for LAF after AF ablation provides comparable acute and long-term success rate but is potentially safer.

Close the gap to get a circle ! The role of visual gaps during circumferential pulmonary vein isolation

This editorial refers to ‘Acute electrical isolation is a necessary but insufficient endpoint for achieving durable PV isolation: the importance of closing the visual gap’ by M.A. Miller et al ., on page 653 Since Michel Haissaguerre in the late 1990 delineated the importance of pulmonary vein (PV) triggers and drivers in the pathogenesis of atrial fibrillation (AF), PV isolation has become the cornerstone of successful interventional treatment of AF.1 Initially, segmental or focal PV disconnection was the main treatment strategy. With the awareness of the role of PV antra in the initiation and maintenance of AF, ablation targets have moved away from isolating PVs inside the atria. Nowadays, circumferential ablation around PVs is the main approach. Different energy sources such as radiofrequency, cryo, and laser have been introduced to produce electrical conduction block between PVs and the atrial tissue by creating precise tissue damage. By placement of a circular ablation line around PVs, these are …

Adenosine-induced atrial tachycardia and multiple foci initiating atrial fibrillation eliminated by catheter ablation using a non-contact mapping system

A 47-year-old male with both atrial tachycardia and atrial fibrillation underwent catheter ablation. During the procedure, rapid administration of adenosine triphosphate induced atrial tachycardia. A non-contact mapping system revealed a focal atrial tachycardia originating from the lateral right atrium, which was successfully ablated. Following the ablation of tachycardia, atrial fibrillation was induced by the injection of adenosine along with multiple extra pulmonary vein foci, which were eliminated by the application of radiofrequency under the guidance of a non-contact mapping system.

Épidémiologie, étiologie et mécanisme de la fibrillation atriale

Atrial fibrillation affects about 750 000 people in France, and its incidence is growing rapidly as the population ages. The main cause used to be rheumatic heart disease, but arterial hypertension is now responsible for about 80 % of cases. The mechanisms are complex. Many cases are due to pulmonary vein foci, but comorbidities can lead to different mechanisms.

Adenosine triphosphate exposes multiple extra pulmonary vein foci of atrial fibrillation

Adenosine triphosphate exposes multiple extra pulmonary vein foci of atrial fibrillation

Focal Ablation versus Single Vein Isolation for Atrial Tachycardia Originating from a Pulmonary Vein

Rapid, disorganized firing from a pulmonary vein (PV) focus may initiate atrial fibrillation. The natural history of PV atrial tachycardia (AT), resulting in a slower, more organized form of firing, is less clear. Furthermore, the optimal therapeutic approach to a PV AT is poorly defined. This study assessed the characteristics and long-term outcomes of focal ablation versus PV isolation for ATs arising from a single PV. We reviewed 886 consecutive patients who underwent an AT radiofrequency ablation at our institution from January 1997 through August 2008. Twenty-six patients had focal AT with a mean cycle length of 364 +/- 90 ms that arose from within a single PV. Ten patients underwent focal ablation of their AT and 16 patients underwent PV isolation of the culprit vein. All procedures were acutely successful. The average follow-up was 25 months (range 2-90 months). There were three recurrences of AT in patients who underwent a focal ablation. There were no recurrences in patients who underwent targeted PV isolation (P = 0.046). No patients developed atrial fibrillation or AT from another focus during the follow-up period. PV AT can be successfully treated with single vein isolation or focal ablation with a low risk of recurrence or the development of atrial fibrillation. PV isolation may be the preferred approach when the AT focus arises from a site distal to the ostium where targeted ablation could result in phrenic nerve injury or occlusion of a pulmonary venous branch.

New insights into mechanisms of atrial fibrillation

Although atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, precise mechanisms that lead to the onset and persistence of AF have not completely been elucidated. Over the last decade, outstanding progress has been made in understanding the complex pathophysiology of AF. The key role of ectopic foci in pulmonary veins as a trigger of AF has been recognized. Furthermore, structural remodeling was identified as the main mechanism for AF persistence, confirming predominant role of atrial fibrosis. Systemic inflammatory state, oxidative stress injury, autonomic balance and neurohormonal activation were discerned as important modifiers that affect AF susceptibility. This new understanding of AF pathophysiology has led to the emergence of novel therapies. Ablative interventions, renin-angiotensin system blockade, modulation of oxidative stress and targeting tissue fibrosis represent new approaches in tackling AF. This review aims to provide a brief summary of novel insights into AF mechanisms and consequent therapeutic strategies.

Multiple Arrhythmogenic Foci Associated With the Development of Perpetuation of Atrial Fibrillation

The presence of multiple arrhythmogenic sources may be associated with the perpetuation of atrial fibrillation (AF). In this study, we investigated the hypothesis that multiple foci might be involved in the development of AF persistency. Two hundred fourteen consecutive patients with AF undergoing catheter ablation were enrolled in this study. The location of the arrhythmogenic foci was determined using simultaneous recordings from multipolar catheters before and after pulmonary vein isolation during an isoproterenol administration. We detected 500 arrhythmogenic foci (263 foci as AF initiators, and 237 foci as non-AF initiators). High-dose isoproterenol infusions (ranging from 2 to 20 microg/min) revealed potential arrhythmogenic foci, especially non-pulmonary vein foci (55%). Persistent AF was more highly associated with an incidence of multiple (>2) foci than paroxysmal AF (88% versus 65%, P=0.002), and a multivariate analysis demonstrated that multiple foci (>2) were an independent contributing factor for persistent AF (odds ratio; 95% confidence interval, 4.69; 1.82 to 12.09, P<0.001). In paroxysmal AF, the number of foci was higher in patients with long-term AF (>24 hours) than in those with short-lasting AF (2.64+/-0.14 versus 1.77+/-0.16, P=0.001). In the persistent AF group, the patients with short-lasting AF (<12 months) had a greater number of foci than did those with long-term AF (>12 months) (3.62+/-0.15 versus 1.92+/-0.16, P=0.04). Multiple foci were likely to be involved in the development of persistent AF. However, if AF persisted for >12 months, they may not have had a significant effect on the AF perpetuation.