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Understanding pulmonary vein (PV) function before and after catheter ablation can validate the benefit of the treatment and provide mechanistic insight into atrial fibrillation (AF). This study was aimed to investigate the functional remodeling process of PVs by multi-detector computed tomography (MDCT). We assessed the dynamic function of four PVs by MDCT at systolic and diastolic phases. Twelve points around each PV ostium were used to assess the magnitude and abnormalities of the regional wall motion. The axis of PV shifting during cardiac cycle was also determined. Seventy-four paroxysmal AF patients and 29 controls were enrolled. In those of AF, the superior PVs had poorer contractile function (ejection fraction: P = 0.01 for left; P = 0.009 for right; magnitude of the motion: P = 0.01 for left; P = 0.02 for right) which mainly resulted from the decreased movement of the posterior wall. In contrast, the function of inferior PVs was similar between two groups. After a mean follow-up of 158 ± 95 days, the PV motion improved in the patients without any AF recurrence. In addition, analysis of the pre-ablation PV function showed that the angles, which shifted during cardiac cycle of left (P = 0.035) and right (P = 0.014) inferior PV, were significantly decreased in recurrent patients. The contractile function of the superior PVs was impaired in paroxysmal AF patients. This was attributed to the hypokinesia of the posterior wall of PVs and improved after circumferential ablation in the patients without recurrence. MDCT images can effectively delineate the functional characteristics of PVs.

Background: Atrial tachycardias (ATs) are commonly observed following catheter ablation of atrial fibrillation (AF). The aim of this study was to identify ECG characteristics that differentiate focal from macroreentrant ATs after circumferential pulmonary vein isolation (CPVI)., Methods and Results: One hundred and twenty ATs that occurred after CPVI were mapped using a 3-dimensional mapping system in 87 patients with AF. Further ablation was performed to eliminate the ATs. The surface ECGs of 68 ATs in 41 consecutive patients (Group 1) were analyzed retrospectively to create diagnostic algorithms. The algorithms were tested in the second 46 consecutive patients (Group 2). Patients with macroreentrant AT had lower left atrial (LA) voltage than those with focal AT (1.3 ± 0.3 vs 1.5 ± 0.2 mV, P = 0.01). Focal AT had a higher incidence of a positive polarity in V6 compared with macroreentrant AT (88% vs 55%, P = 0.03). The positive amplitude of the flutter/P waves in V6 was higher for focal AT than macroreentrant AT. The cycle lengths of the focal ATs were longer than those for macroreentrant AT (296 ± 107 vs 244 ± 25 ms, P < 0.001). Right atrial macroreentrant AT had a higher incidence of a negative polarity in at least 1 precordial lead compared with LA macroreentry. The positive flutter waves in V1 could differentiate roof/mitral isthmus dependent from non-roof/mitral isthmus dependent macroreentry. This algorithm correctly differentiated the focal from macroreentrant ATs with a sensitivity of 94%, specificity of 91%, and predictive accuracy of 92% in Group 2., Conclusion: Different electrophysiological properties may facilitate the differentiation between macroreentrant and focal ATs after CPVI., (© 2011 Wiley Periodicals, Inc.)

Introduction: The relationship between pulmonary veins (PVs) with atrial fibrillation (AF) initiating triggers and their surrounding atrial substrate has not been elucidated. We aimed to clarify the atrial substrate properties around the PVs., Methods and Results: Twenty-three paroxysmal AF patients were studied with the identification of PV initiating triggers. High-density mapping of the dominant frequency (DF, 1200 Hz) and the mean degree of the complex fractionated electrograms (CFE mean interval over 6 seconds) was evaluated in 2 zones (zone 1: < 5 mm, zone 2: 5-15 mm from the PVs) and the left atrial (LA) using a NavX system prior to the PV isolation. High-DFs (>8 Hz) and continuous CFEs (<50 ms) were identified in 1.5 ± 0.9 and 2.3 ± 1.1 regions per patient, respectively. Most of the high-DF regions (86%) and continuous CFE regions (77%) were located within 15 mm of the PV ostia. Of those, 75% of the high-DF regions and 54% of the continuous CFE regions were related to arrhythmogenic PVs. There was a significant DF gradient from arrhythmogenic PV zone 1 to zone 2, while the mean CFE exhibited a significant gradient between arrhythmogenic PV zone 2 and the rest of the LA. Additionally, 69% of the procedural AF termination sites were at arrhythmogenic PV zone 2., Conclusion: Evaluation of the atrial substrate properties may be useful for locating arrhythmogenic PVs during AF and defining the extent of the circumferential PV isolation., (© 2010 Wiley Periodicals, Inc.)

Aims: Additional ablation in the pulmonary vein (PV) carina region is sometimes required to achieve electrical isolation following circumferential pulmonary vein isolation (PVI). This study investigated the procedural predictors for the requirement of additional carina ablation to achieve complete electrical isolation with PVI., Methods and Results: Eighty patients with drug-refractory paroxysmal AF underwent circumferential PVI. After the first round of PVI, we placed circular catheters inside the veins to identify the residual PV potentials, and also performed electroanatomic mapping to observe the earliest activation sites during sinus rhythm. The requirement of an additional gap and carina ablation, and the optimal distance that predicted an incomplete PV block were assessed. In the first 40 patients, 43% of the ipsilateral PVs were electrically isolated after the initial PVI. Subsequent ablation of the gaps and ablation of the carina were required in the remaining 57% PVs. The only predictor of the requirement of carina ablation was the mean distance between the lesion-related scar and the ostia (P = 0.03). The longer the distance from the isolating lesions to the PV ostia (>8 mm) predicted an incomplete PV isolation after the first round of circumferential isolation. In the next 40 patients, a fixed distance of 8 mm to the PV ostia decreased the requirement of a carina ablation and resulted in a shorter procedure time (P < 0.05)., Conclusions: This study indicated the importance of complete linear lesions and additional carina ablation when the wide area circumferential PV isolation was applied.

Background: Previous studies have indicated that atrial fibrillation (AF) in patients over the age of 60 at diagnosis is a risk factor for a substantial increase in cardiovascular events. However, information about the impact of age on the atrial substrate and clinical outcome after catheter ablation of AF is limited., Methods: This study included 350 patients (53 ± 12 years, 254 males) who underwent circumferential pulmonary vein isolation (CPVI) of AF, guided by a NavX mapping system. The subjects were divided into three groups according to their age, as follows: Group I: age ≤50 (n = 141), Group II: age = 51-64 (n = 149) and Group III: age ≥65 years old (n = 60). The mean voltage and total activation time of the individual atria were obtained by using a NavX mapping system before ablation. Several parameters, including the gender, AF duration, and left atrial (LA) diameter were analyzed., Results: The younger age group had a significantly smaller LA diameter (Group I vs Group II vs Group III, 36.89 ± 7.11 vs 39.16 ± 5.65 vs 40.77 ± 4.95 mm, P = 0.002) and higher LA bipolar voltage (2.09 ± 0.83 vs 1.73 ± 0.73 vs 1.86 ± 0.67 mV, respectively, P = 0.024), compared with the older AF patients. The LA bipolar voltage exhibited a significant reduction when the patients became older, however, that did not occur in the right atrium. The incidence of an AF recurrence was higher in the older age group than in the younger age groups. A subgroup of patients with lone AF was analyzed and age was found to be an independent predictor of the AF recurrence after receiving the first CPVI in the multivariable model (P < 0.05)., Conclusions: Age has a significant impact on the LA substrate properties and outcome of the catheter ablation of AF., (© 2010 Wiley Periodicals, Inc.)

Introduction: Although several studies have reported the benefits of cooled-tip ablation for circumferential pulmonary veins isolation (CPVI), the acute change of substrate property and acute PV reconnection have not been well demonstrated. The aim of this study was to compare the cooled-tip with regular 4-mm-tip catheter in acute substrate change after CPVI and long-term efficacy., Methods and Results: One hundred and fifty-six patients (115 males, age 53 +/- 12 years) who underwent CPVI for treatment of atrial fibrillation (AF) were included. Group A consisted of 52 patients with cooled-tip ablation, and group B consisted of 104 patients with 4-mm-tip catheter ablation. The bipolar voltage of circumferential lesions was obtained using a 3-dimensional (3D) mapping system (NavX) before and after CPVI. The electrical reconnections of 4 PVs were evaluated 30 minutes after CPVI using a circular catheter. Cooled-tip catheter caused more reduction of the electrical voltage in PV antrum, lower incidence of acute PV reconnection, inducibility of AF, and gap-related atrial tachyarrhythmia (AT). Less number of left atrial (LA) ablation line and ablation applications and less procedure time were found in cooled-tip group compared to 4-mm-tip group. No significant difference in the incidence of pain sensation and complication was observed between the 2 groups. At a 14-month follow-up, the recurrence rate in the cooled-tip group was lower than in the 4-mm group (13.5% vs 33.7%, P = 0.009)., Conclusion: Cooled-tip catheter has a superior long-term outcome than the 4-mm-tip catheter in CPVI, which may be associated with the efficacy of transmural block and electrical isolation in PV antrum.

Introduction: The left atrial (LA) substrate plays an important role in the maintenance of atrial fibrillation (AF). However, little is known about the acute effect of circumferential pulmonary vein isolation (CPVI). This study was to investigate the acute change of LA activation, voltage and P wave in surface electrocardiogram (ECG) after CPVI., Methods and Results: Electroanatomic mapping (NavX) was performed in 50 patients with AF (mean age = 54 +/- 10 years, 36 males) who underwent only CPVI. The mean peak-to-peak bipolar voltage and total activation time of LA were obtained during sinus rhythm before and immediately after CPVI. The average duration and amplitude of P waves in 12-lead ECG were also analyzed before and after CPVI. Change in the earliest LA breakthrough sites could cause decreased LA total activation time. Downward shift in the breakthrough site was inversely proportional to the proximity of the breakthrough site to the radiofrequency lesions. A shortening of P-wave duration and decrease in voltage after CPVI were observed after CPVI. Patients with recurrent AF had less voltage reduction in the atrial wall 1 cm from the circumferential PV lesions compared with those without recurrent AF (60.1 +/- 11.7% vs 74.1 +/- 6.6%, P = 0.002). Reduction of voltage < or = 64.4% in this area after CPVI is related with recurrent AF., Conclusion: CPVI could result in acute change of LA substrate, involving LA activation and voltage. Less reduction of voltage in the atrial wall adjacent to the circumferential PV lesions after CPVI may be associated to the recurrence of AF.

Introduction: Atrial tachycardia (AT), including focal and reentrant AT, can occur after circumferential pulmonary vein isolation (CPVI). The aim of this study was to investigate the electrophysiological characteristics of induced AT and its clinical outcome., Methods and Results: In our series of 160 patients with paroxysmal atrial fibrillation (AF), 45 ATs were induced by high-current burst pacing after CPVI in 26 patients. All induced ATs were mapped using a three-dimensional (3D) mapping system. Noninducibility was the endpoint of the ablation of the AT. Gap-related AT was considered if the AT was related to the CPVI lesions. A 16-slice multidetector computed tomography scan was performed in all patients to correlate the anatomical structure with electroanatomical mapping. Thirty-five (78%) reentrant ATs and 10 (22%) focal ATs were identified. Of those, 34 were gap-related ATs (24 reentrant and 10 focal ATs). Reentrant AT had more gaps in the left atrial appendage ridge than did focal AT (39.6% vs 0%, P = 0.02). Focal AT had a higher incidence of gap in the PV carina compared with reentrant AT (80% vs 10%, P < 0.001). Reentrant ATs were mostly terminated during the ablation creating the mitral and roof lines with crossing of the gaps. During a mean follow-up of 21 +/- 8 months, only one patient (0.6%) with induced mitral reentry had a recurrent AT., Conclusion: The location of the AT gap may be related with the complex anatomy of the LA. The induced ATs after CPVI can be eliminated by catheter ablation.

Objectives and Background: The success rate of achieving electrical isolation by circumferential pulmonary vein ablation (CPVA) varies from 32% to 88%. We carried out ablation at the pulmonary vein carina to evaluate the elimination rates of the pulmonary vein potentials (PVPs) after one round of CPVA had failed to eliminate all the PVPs in the patients with atrial fibrillation (AF)., Methods: Ninety-seven patients (75 males; mean age: 50 +/- 12 years; 15 with persistent AF and 82 with paroxysmal AF) who underwent catheter ablation were analyzed. All patients underwent one round of CPVA with PVP elimination as the endpoint. The electrophysiology tracings were then analyzed to look for the presence of any gaps that were subsequently targeted by radiofrequency ablation. The patients in whom the PVPs still persisted underwent ablation at the pulmonary vein carina and the success rate of the PVP elimination was studied. The patients were followed up for a mean duration of 12.9 +/- 8.2 months., Results: One hundred ninety-four ipsilateral pulmonary veins in 97 patients were subjected to CPVA with successful elimination of the PVPs in 110 ipsilateral pulmonary veins (success rate of 56.7%). A carina ablation was carried out in the remaining 84 ipsilateral pulmonary vein pairs harboring PVPs. Elimination of the PVPs was achieved in all the remaining ipsilateral pulmonary veins after the carina ablation., Conclusion: Considering the limited efficacy of CPVA in eliminating the PVPs, pulmonary vein carina ablation is advisable to substantially increase the PVP elimination rate.

Introduction: Atrio-bronchial fistula (ABF) can be a rare but potentially lethal complication following the catheter ablation of atrial fibrillation (AF). Understanding the extent of the contact between the bronchial tree and pulmonary veins (PVs) is critical to avoid this complication. We investigated the anatomic relationship between the four PVs and bronchial tree using multi-detector computed tomography (MDCT) images., Methods and Results: Seventy patients with drug refractory AF were included. They underwent 16-slice MDCT before the ablation. The spatial relationship between the bronchus and PVs was demonstrated by the multi-planar images. The bronchus was in direct contact with four PVs in the vast majority of patients. The mean distances between the bronchus and the ostia of right superior, left superior, right inferior, and left inferior PV were 7.1 +/- 5.5, 3.5 +/- 4.8, 12.3 +/- 5.6, and 17.9 +/- 6.8 mm, respectively. Patients were categorized into two groups: Group I: proximal contact (<5 mm from the PV ostium) and Group II: distal contact (>5 mm from the PV ostium). For the right superior pulmonary vein (RSPV), the Group I patients were associated with thinner connective tissue between them (P = 0.001), a larger RSPV (17.2 +/- 2.2 vs 15.5 +/- 2.1 mm, P < 0.001), and right inferior pulmonary vein (RIPV) diameter (15.9 +/- 1.9 vs 14.6 +/- 1.6 mm, P < 0.01). For the left superior pulmonary vein (LSPV), the Group I patients were associated with an older age (P = 0.02)., Conclusion: Isolation of the superior PVs may carry the potential risk of bronchial damage. The clinical or anatomic characteristics associated with the proximal contact between the bronchi and superior PVs can provide useful information to prevent this complication.

Background: Electrical isolation of pulmonary veins (PVs) is an effective therapy for atrial fibrillation (AF). Both segmental ostial PV ablation and circumferential ablation with PV-left atrial (LA) block have been implicated to eliminate AF. However, the mechanism of the recurrent AF after undergoing either strategy remains unclear., Methods and Results: Of the 73 consecutive patients with symptomatic AF that underwent PV isolation and had recurrences of AF, Group 1 consisted of 46 patients (age 56 +/- 13 years old, 35 males) who underwent PV isolation by segmental ostial PV ablation and Group 2 consisted of 27 patients (age 51 +/- 11 years old, 24 males) who underwent circumferential ablation with PV-LA block. In Group 1, the earliest ectopic beat or ostial PV potentials were targeted. In Group 2, circumferential ablation with PV-LA block was performed by encircling the extraostial regions around the left and right PVs. During the first procedure, all patients had PV-AF. There was no difference in the non-PV ectopy between Group 1 and Group 2. During the second procedure, the incidence of an LA posterior wall ectopy initiating AF was significantly lower (20% vs. 0%, P = 0.01) in Group 2. There was no difference in the PV ectopy initiating AF during the second procedure., Conclusion: Circumferential ablation of AF with PV-LA block may eliminate the LA posterior wall ectopy and decrease the incidence of LA posterior wall ectopy initiating AF during the second procedure.

Introduction: Some conflicting results of the efficacy of the inducibility test used in the catheter ablation of atrial fibrillation (AF) have been reported. The aim of this study was to investigate the inducibility and efficacy of circumferential ablation with pulmonary vein isolation (PVI) in patients with paroxysmal AF and its relationship to the atrial substrate., Methods and Results: This study consisted of 88 patients with paroxysmal AF who underwent catheter ablation. Electroanatomic mapping using a NavX system was performed and the biatrial voltage was obtained during sinus rhythm. After successful circumferential ablation with PVI, an inducibility test was performed to determine the requirement for creating left atrial (LA) ablation line. After procedure, patients with inducible AF had a higher recurrence rate than did those with noninducibility of AF (55% vs 18%, P = 0.02). The patients with inducible AF after the PVI had a lower biatrial voltage than did those with negative inducibility. The patients with inducible AF after the final procedure who had a recurrence had a lower LA voltage (1.3 +/- 0.4 vs 1.8 +/- 0.4 mV, P = 0.02) and longer LA total activation time (99 +/- 18 vs 88 +/- 13 msec, P = 0.02) than did those with noninducible AF and no recurrence. None of the patients had occurrence of LA flutter during the follow-up., Conclusion: After a single procedure of circumferential ablation with PVI and noninducibility, 82% patients did not have recurrence of AF. The inducibility of AF was related to the recurrence of AF. The atrial substrate affected the outcome of the inducibility.

Inflammation and abnormal calcium homeostasis play important roles in atrial fibrillation. Tumor necrosis factor-alpha (TNFalpha), a proinflammatory cytokine, can induce cardiac arrhythmias. Pulmonary veins (PVs) are critical in initiating paroxysmal atrial fibrillation. This study was designed to investigate whether TNFalpha may change the calcium handling and arrhythmogenic activity of PV cardiomyocytes. We used whole-cell patch clamp and indo-1 fluorimetric ratio technique to investigate the action potentials, ionic currents and intracellular calcium in isolated rabbit single PV cardiomyocytes with and without (control) incubation with TNFalpha (25 ng/ml) for 7-10 h. The expression of sarcoplasmic reticulum ATPase in the control and TNFalpha-treated PV cardiomyocytes was evaluated by confocal micrographs and Western blot. We found that the spontaneous beating rates were similar between the control (n=45) and TNFalpha-treated (n=28) PV cardiomyocytes. Compared with the control PV cardiomyocytes, the TNFalpha-treated PV cardiomyocytes had significantly a larger amplitude of the delayed afterdepolarizations (6.0+/-1.7 vs. 2.6+/-0.8 mV, P<0.05), smaller L-type calcium currents, larger transient inward currents, larger Na(+)-Ca(2+) exchanger currents, a smaller intracellular calcium transient, smaller sarcoplasmic reticulum calcium content, larger diastolic intracellular calcium, a longer decay portion of the calcium transient (Tau), and a decreased sarcoplasmic reticulum ATPase expression. In conclusion, TNFalpha can increase the PV arrhythmogenicity and induce an abnormal calcium homeostasis, thereby causing inflammation-related atrial fibrillation.

Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 microM) inhibited the automatic rhythm. Losartan (10 microM) prolonged the AP duration and reduced the contractile force (1 and 10 microM). Angiotensin II reduced the transient outward potassium current (I(to)) but increased the L-type calcium, delayed rectifier potassium (I(K)), transient inward (I(ti)), pacemaker, and Na(+)-Ca(2+) exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the I(to), I(K), I(ti), and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation.

Introduction: The structural changes of the superior caval vein, pulmonary veins, and left atrium in atrial fibrillation initiated by superior caval vein ectopy have not been reported., Methods and Results: Nine patients with atrial fibrillation initiated by superior caval vein ectopic beats (male = 5, 54 +/- 10 years) and 15 control (n = 15, male = 10, 52 +/- 8 years) without any cardiac arrhythmias were included in this study. Using gadolinium-enhanced magnetic resonant angiography with three-dimensional reconstruction, the parameters of the superior caval vein morphology (length, various diameters, area, eccentricity, and volume) were measured. The morphological parameters of the four pulmonary veins (diameter, ostial area, and eccentricity) were also measured at the pulmonary vein-left atrial junction in an oblique sagittal section from the multiple-plane reconstruction images. The left atrial diameters and volume were measured. The different morphological parameters were compared between the two groups. The patients with atrial fibrillation initiated by superior caval vein ectopic beats exhibited a more eccentric structure of the second part of the superior caval vein as compared to the control group. All the ectopic beats initiating atrial fibrillation were located in the second part of the superior caval vein. Furthermore, the patients with atrial fibrillation initiated by superior caval vein ectopic beats had a larger superior caval vein volume, left atrial volume, and pulmonary vein size, and more eccentric pulmonary vein ostia than the controls., Conclusion: Structural changes of the superior caval vein were demonstrated in the patients with atrial fibrillation initiated by superior caval vein ectopic beats. These findings might explain the arrhythmogenic mechanism of atrial fibrillation initiated by superior caval vein ectopy.

Introduction: Understanding the structural remodeling and reverse remodeling of the left atrium (LA) and pulmonary vein (PV) after radiofrequency ablation of atrial fibrillation (AF) may provide important insights into the mechanism and management of AF. This study used magnetic resonance angiographic (MRA) images to investigate changes in PV and LA morphologies before and more than 1 year after ablation., Method and Results: Forty-five patients (36 men and 9 women, mean age 60 +/- 13 years) who underwent MRA before and more than 12 months (mean 21 +/- 11) after ablation of paroxysmal AF were included in the study. The patients were divided into two groups: group I included 35 patients without AF recurrence, and group II included 10 patients with late (>1 month postablation) recurrence of AF. The sizes of the LA and nonablated PV were compared before and after ablation. In group I, significant reduction of ostial area of both superior PVs was noted (left superior PV: from 2.85 +/- 0.67 to 2.59 +/- 0.73 cm2; right superior PV: from 2.89 +/- 0.85 to 2.60 +/- 0.73 cm2, both P <0.001). Geometric alteration toward a round shape was noted in the ostia of superior PVs during follow-up (eccentricity of right superior PV and left superior PV decreased from 0.31 +/- 0.10 to 0.22 +/- 0.13 and from 0.27 +/- 0.11 to 0.19 +/- 0.13, respectively, both P <0.01). However, LA volume showed only borderline reduction (from 61.52 +/- 19.06 to 56.64 +/- 17.13 mL, P=0.05). In group II, significant dilation of the LA (from 61.14 +/- 17.54 to 78.73 +/- 25.27 mL, P=0.004) and right superior PV (from 3.41 +/- 1.12 to 4.08 +/- 1.31 cm2, P=0.016) was noted during follow-up. Ostial area and eccentricity of the left superior, left inferior, and right inferior PVs and LA were similar before and after ablation., Conclusion: Structural remodeling of the superior PVs and LA can be reversible after successful ablation without AF recurrence; however, late recurrence of AF is associated with progressive LA dilation.

A 71-year-old male patient was admitted for catheter ablation of the pulmonary veins to treat paroxysmal atrial fibrillation. Atrial fibrillation originating from the left superior pulmonary vein was induced after a pause of atrial pacing under isoproterenol infusion and became sustained. Spontaneous transition from atrial fibrillation to typical atrial flutter was noted after complete isolation of the pulmonary vein focus from the left atrium. Subsequently linear ablation of the cavotricuspid isthmus was created with completely bi-directional isthmus conduction block. We hypothesized that ectopic pulmonary vein focus played an important role in the spontaneous conversion of atrial fibrillation to typical atrial flutter, and complete isolation of the pulmonary vein could stop the spontaneous transition between the two atrial tachyarrhythmias.

Introduction: Pulmonary veins (PVs) are known to initiate paroxysmal atrial fibrillation. T-type calcium current (I(Ca-T)) has a role in normal and abnormal automaticity of cardiomyocytes. The aim of this study was to evaluate whether I(Ca-T) contributes to PV electrical activity., Methods and Results: By whole-cell clamp techniques in rabbit myocytes, I(Ca-T) was identified in 12 (39%) of 31 PV cardiomyocytes with pacemaker activity, 2 (9%) of 23 PV cardiomyocytes without pacemaker activity, and 2 (15%) of 13 atrial myocytes (P < 0.05). Maximum I(Ca-L) and I(Ca-T) densities from PV cardiomyocytes with pacemaker activity were 6.87 +/- 2.17 pA/pF and 1.38 +/- 0.69 pA/pF, respectively. Nickel (40 microM) decreased the spontaneous activity in 5 (36%) of 14 PV cardiomyocytes (3.1 +/- 0.6 Hz vs 2.2 +/- 0.5 Hz, P < 0.05), reduced the amplitudes of delayed after depolarization from 13 +/- 1 mV to 7 +/- 1 mV (n = 4, P < 0.05) and inhibited transient inward currents from 1.2 +/- 0.2 pA/pF to 0.7 +/- 0.1 pA/pF (n = 11, P < 0.01)., Conclusions: We conclude that I(Ca-T) contributes to PV pacemaker activity and triggered activity, which are of functional importance in PV arrhythmogenesis.

Ethanol consumption has been considered to contribute to the occurrences of paroxysmal atrial fibrillation. Pulmonary veins are known to initiate atrial fibrillation. This study investigated whether ethanol may induce atrial fibrillation through increasing arrhythmogenic activity of pulmonary vein cardiomyocytes. Using the whole-cell clamp technique, the action potential and ionic currents were investigated in rabbit single pulmonary vein beating cardiomyocytes with and without (control) incubation of ethanol. Compared with control cardiomyocytes, pulmonary vein cardiomyocytes receiving 0.3 mg/ml or 1 mg/ml ethanol had shorter action potential duration, but had similar beating rates (2.6+/-1.3, 2.7+/-1.2, 2.7+/-1.2 Hz) and incidences (45%, 41%, 32%) of delayed after depolarization. Pulmonary vein cardiomyocytes receiving ethanol had smaller L-type Ca(2+) currents and larger transient outward currents, but had similar transient inward, delayed rectified outward, inward rectified and pacemaker currents. These results suggest that ethanol has no direct effect on the arrhythmogenic potential of pulmonary vein cardiomyocytes.

Background: Most of the ectopic beats initiating paroxysmal atrial fibrillation (PAF) originate from the pulmonary vein (PV). However, only limited data are available on PAF originating from the non-PV areas., Methods and Results: Two hundred forty patients with a total of 358 ectopic foci initiating PAF were included. Sixty-eight (28%) patients had AF initiated by ectopic beats (73 foci, 20%) from the non-PV areas, including the left atrial posterior free wall (28, 38.3%), superior vena cava (27, 37.0%), crista terminalis (10, 3.7%), ligament of Marshall (6, 8.2%), coronary sinus ostium (1, 1.4%), and interatrial septum (1, 1.4%). Catheter ablation eliminated AF with acute success rates of 63%, 96%, 100%, 50%, 100%, and 0% in left atrial posterior free wall, superior vena cava, crista terminalis, ligament of Marshall, coronary sinus ostium, and interatrial septum, respectively. During a follow-up period of 22+/-11 months, 43 patients (63.2%) were free of antiarrhythmic drugs without AF recurrence., Conclusions: Ectopic beats initiating PAF can originate from the non-PV areas, and catheter ablation of the non-PV ectopy has a moderate efficacy in treatment of PAF.

The basic electrophysiologic studies have proved the arrhythmogenic mechanisms of the pulmonary vein as an atrial fibrillation initiator; the mechanisms include enhanced automaticity, triggered activity, and microreentry from myocardial sleeves inside pulmonary veins. Immunohistology study has proved the conduction characteristics of pulmonary vein myocardium, and further study of ionic currents are important for understanding atrial fibrillation initiation from the pulmonary vein.

Introduction: The superior vena cava (SVC) and right superior pulmonary vein (RSPV) are anatomically close structures. Using 12-lead ECG may facilitate identification of ectopic foci from SVC or RSPV. The aim of this study was to assess whether P wave polarity on surface ECG is helpful in distinguishing an arrhythmogenic focus of paroxysmal atrial fibrillation (AF) from SVC or RSPV., Methods and Results: Thirty-four patients with paroxysmal AF from the SVC (group I: 17 patients, 10 men and 7 women; mean age 57 +/- 12 years) or RSPV (group II: 17 patients, 15 men and 2 women, mean age 62 +/- 14 years) underwent electrophysiologic study and radiofrequency (RF) catheter ablation. All of the AF foci were confirmed by successful ablation. P wave polarities on surface ECG inferior leads were positive during sinus rhythm and ectopic beats in both groups. Leads I, aVR, aVL, and V1 were further analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in predicting an arrhythmogenic focus of AF from SVC or RSPV were provided. P wave polarity in lead aVR was negative in all 34 patients. P wave polarity in lead V1 was positive in 47.1% of SVC ectopy but positive in all RSPV ectopy. The combination of a biphasic or isoelectric P wave polarity in lead V1 or a biphasic P wave polarity in lead aVL had a sensitivity of 71%, specificity of 82%, PPV of 80%, and NPV of 74% in predicting an arrhythmogenic focus of AF from SVC., Conclusion: P wave polarity in leads V1 and aVL may predict an arrhythmogenic focus of AF from SVC or RSPV.

Several investigators have identified the pulmonary vein as the most common initiator of atrial fibrillation, and isolation of the pulmonary vein from atrial tissue can cure approximately 70% of patients with paroxysmal atrial fibrillation. Ongoing trials of a new device may increase the success rate and decrease the complication rate during the pulmonary vein isolation procedure.

Abstract: Introduction: Lone atrial fibrillation (AF) is defined as AF occurring in the absence of any other cardiovascular disease. The prognosis of patients with lone AF varies in previous studies, and the clinical and electroanatomical characteristics of lone AF are unclear. The purpose of this study was to investigate the clinical characteristics of lone AF. Methods: This study included 203 patients (52±13 years old, 144 males) that underwent circumferential pulmonary vein isolation (CPVI) for paroxysmal AF. The mean voltage and total activation time of the individual atria were obtained by using a NavX mapping system and were compared for patients with lone and non-lone AF. Several parameters, including the age, gender, AF duration, and left atrial (LA) diameter were analyzed. Results: Compared with non-lone AF patients, lone AF patients were significantly younger (49±13 years old vs. 58±11 years old, p<0.001) and had lower body-mass index (BMI, 24.60±2.96 vs. 26.07±3.29, p=0.02), lesser cholesterol level (169.06±31.41 vs. 183.63±31.12, p=0.014), smaller LA diameter (35.89±4.90 vs. 40.86±4.62, p<0.001), and higher LA bipolar voltage (2.10±0.50 vs. 1.83±0.73mV, p<0.05). Furthermore, a dramatic voltage reduction was observed for 60-year-old patients. Conclusion: Patients with lone AF have unique clinical and electroanatomical characteristics. [Copyright &y& Elsevier]

Very Early Recurrence of AF. Introduction: Early restoration of sinus rhythm following ablation of atrial fibrillation (AF) facilitates reverse atrial remodeling and improves the long-term outcome. The purpose of this study was to determine the predictors and outcome in patients with very early AF recurrences (< 2 days). Methods and Results: Ablation was performed in 339 consecutive AF patients (paroxysmal AF = 262). Biatrial voltage was mapped during sinus rhythm. If recurrent AF occurred within 2 days following the ablation, electrical cardioversion was performed to restore sinus rhythm. Very early recurrences of AF occurred in 39 (15%) patients with paroxysmal AF and 26 (34%) with nonparoxysmal AF. Patients with very early recurrence had a higher incidence of nonparoxysmal AF (40% vs 18.6%, P< 0.001), requirement of electrical cardioversion during procedure, larger left atrial (LA) diameter (43 ± 7 vs 39 ± 6 mm, P< 0.001), lower left ventricular ejection fraction (54 ± 10% vs 59 ± 7, P< 0.001), longer procedural time, and lower LA voltage (1.5 ± 0.7 vs 1.9 ± 0.8 mV, P< 0.001). A multivariate analysis revealed that the independent predictors of a very early recurrence were a longer procedural time and lower LA voltage. During a follow-up of 13 ± 5 months, a very early recurrence did not predict the long-term outcome of a single procedure recurrence in the patients with paroxysmal AF, but was associated with a late recurrence in the nonparoxysmal AF patients. Conclusion: Very early recurrence occurred in patients with paroxysmal AF is not associated with long-term recurrence. Nonparoxysmal AF is an independent predictor of late recurrence of AF in patients with very early recurrence. (J Cardiovasc Electrophysiol, Vol. pp. 1-6) [ABSTRACT FROM AUTHOR]

Background: The left atrial (LA) size is an important predictor of atrial fibrillation (AF) procedural termination and the long-term outcome. We sought to evaluate the long-term outcome in regard to the LA size and procedural termination. Methods: Eighty-seven consecutive chronic AF patients (72 males, 53 ± 10 years) underwent 3D mapping (NavX) and ablation. A stepwise approach including circumferential pulmonary vein (PV) isolation, linear ablation, and continuous complex-fractionated electrogram (CFE) ablation (targeting fractionation intervals of < 50 ms). Electrical cardioversion was applied to those without any procedural termination. The freedom from AF was defined as the maintenance of sinus rhythm without the use of any class I or III antiarrhythmic drugs after the blanking period. Results: Among the 87 patients, all received a circumferential PV isolation, 93% a linear ablation, and 59% a continuous CFE ablation. Those with AF procedural termination (n = 30) had a better long-term outcome when compared with those without termination during a follow-up of 21 ± 12 months. Moreover, a Kaplan-Meier analysis showed that in those with an LA diameter of less than 45 mm (n = 49), the freedom from AF rate was higher when procedural termination was achieved (P = 0.004). On the contrary, the outcome was comparable in those with an LA diameter of ≥ 45 mm (n = 38), whether AF procedural termination occurred or not (P = 0.658). Conclusions: AF procedural termination was related to the long-term success during chronic AF ablation, especially in those with an LA diameter of less than 45 mm. The favorable effect of termination decreased when the LA diameter was ≥ 45 mm. [ABSTRACT FROM AUTHOR]

Background: The characteristics of cavotricuspid isthmus (CTI) in patients with atrial fibrillation (AF) and flutter that may predict recurrence of flutter is not known. We aimed to investigate the CTI characteristics in patients who underwent a second ablation procedure for recurrent AF after previous combined pulmonary vein (PV) and CTI ablation. Methods: Among 196 consecutive patients with drug-refractory symptomatic AF who underwent PV isolation and CTI ablation with bidirectional isthmus block, 49 patients (age 50 ± 12 years, 43 males) had recurrent AF and received a second procedure 291 ± 241 days after the first procedure. Right atrial angiography for the evaluation of the CTI morphology, and the biatrial contact bipolar electrograms were obtained before both procedures. Results: In the second procedure, 11 (group 1) of the 49 patients demonstrated recovered CTI conduction. Compared with the patients without CTI conduction (group 2, n = 38), group 1 patients had a higher frequency of a pouch-type anatomy (82% vs 13%, P < 0.001), longer CTI (34.0 ± 8.6 vs 25.5 ± 7.5 mm, P = 0.01), longer ablation time, and larger number of radiofrequency applications; furthermore, the preablation bipolar voltage decreased along both the CTI and ablation line in group 2, whereas it remained similar in group 1 in the second procedure. Conclusions: A high (22%) percentage of CTIs exhibited recurrent conduction in the long-term follow-up. The CTIs with recurrent conduction had a higher incidence of a pouch and longer length compared with those without recurrent conduction. [ABSTRACT FROM AUTHOR]

Background: The features of multiple catheter ablation procedures for paroxysmal atrial fibrillation (AF) are unknown. We aimed to investigate the electrophysiologic characteristics and the clinical outcomes in the patients with AF who received more than two ablation procedures. Methods: The study consisted of 15 consecutive patients (age 48 ± 14 years, 10 males) who had undergone three to five (3.3 ± 0.6) catheter ablation procedures for recurrent paroxysmal AF. Results: Ten patients had pulmonary vein (PV)-AF and one had AF originating from both PVs and the superior vena cava (SVC) in the first ablation procedure. All of them exhibited PV reconnection during the recurrent episodes. Four of the 15 patients had AF originating from non-PV foci (three from the SVC, one from the crista terminalis) in the first procedure, and two had AF recurrences due to recovered conduction from the SVC. In all patients with PV-AF recurrences, repeated PV isolation procedures could effectively eliminate the AF. The incidence of the need for additional LA linear ablation lesions was higher comparing between the first procedure and in the following ablation procedures (18% vs. 71%, P = 0.02). During a follow-up of 1.7 ± 1.1 years, 73% of the patients remained in sinus rhythm without any antiarrhythmic drugs after the final procedure. Conclusions: Recovered PV connection was the major cause of the AF recurrences despite undergoing multiple catheter ablation procedures. It is advisable to inspect all PVs during the AF recurrence. Repeated PV isolation plus left atrial linear ablations could effectively eliminate the AF with satisfactory outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The left atrial appendage (LAA) has been proven to be the most important site of thrombus formation in patients with atrial fibrillation (AF). However, the information regarding the morphometric alteration of the LAA related to the outcome of AF ablation is still lacking. Thus, we evaluated the long-term changes of the LAA morphology in patients undergoing catheter ablation of AF using magnetic resonance angiography (MRA). Methods and Results: Group 1 included 15 controls without any AF history. Group 2 included 40 patients with drug-refractory paroxysmal AF. They were divided into two subgroups: group 2a included 30 patients without AF recurrence after pulmonary vein (PV) ablation. Group 2b included 10 patients with late recurrence of AF. The LAA morphology before and after (20 ± 11 months) ablation was evaluated by three-dimensional MRA. The group 2 patients had a larger baseline LAA size (including the LAA orifice, neck, and length) and less eccentric LAA orifice and neck. After the AF ablation, there was a significant reduction in the LAA size in the group 2a patients, and the morphology of the LAA neck became more eccentric during the follow-up period. In group 2b, the LAA size increased and no significant change in the eccentricity of the orifice and neck could be noted. Conclusions: The morphometric remodeling of the LAA in the AF patients could be reversed after a successful ablation of the AF. Progressive dilation of the LAA was noted in the patients with AF recurrence. These structural changes in the LAA may play a role in reducing the potential risk of cerebrovascular accidents. [ABSTRACT FROM AUTHOR]

Conventional atrial fibrillation (AF) mapping is limited by the interpretation of the varied and complex time-domain signals throughout the atria. Frequency-domain signals provide a feasible method to analyze the temporal and regional distribution of atrial activation during AF. This helps us learn more about the mechanisms of AF. The maintenance of AF, whether paroxysmal or persistent, depends on rapid activities in part of the atrium. These AF sources activate atria at very high frequencies and result in fibrillatory conductions. This article focuses on the regional frequency distribution and the spectral morphology in different types of AF. In patients with paroxysmal AF from pulmonary veins, the highest frequency drivers are located around the arrhythmogenic vein with a left atrium (LA)-to-right atrium (RA) frequency gradient. Conversely, in patients with paroxysmal AF from superior vena cava and persistent AF, the LA-to-RA frequency gradient may not be evident. As the figure demonstrates, the ablation strategy guided by frequency analysis may be a better way for finding the critical substrate for the maintenance of AF. [ABSTRACT FROM AUTHOR]

Introduction: The mechanisms of late (<1 year after the ablation) and very late (>1 year after the ablation) recurrences of paroxysmal atrial fibrillation (AF) after catheter ablation have not been reported. Methods and Results: Fifty consecutive patients undergoing a repeated electrophysiologic study to investigate the recurrence of paroxysmal AF after the first ablation were included. Group 1 consisted of 12 patients with very late (26 ± 13 months) and group 2 consisted of 38 patients with late (3 ± 3 months) recurrence of paroxysmal AF. In the baseline study, group 1 had a lower incidence of AF foci from the pulmonary veins (PVs) (67% vs 92%, P = 0.048) and a higher incidence of AF foci from the right atrium (50% vs 13%, P = 0.014) than group 2. In the repeated study, group 1 had a higher incidence of AF foci from the right atrium (67% vs 3%, P < 0.001) and a lower incidence of AF foci from the left atrium (50% vs 97%, P < 0.001), including a lower incidence of AF foci from the PVs (50% vs 79%, P = 0.07) and from the left atrial free wall (0% vs 29%, P = 0.046) than group 2. Furthermore, most of these AF foci (64% of group 1, 65% of group 2) were from the previously targeted foci. Conclusion: The right atrial foci played an important role in the very late recurrence of AF, whereas the left atrial foci (the majority were PVs) were the major origin of the late recurrence of AF after the catheter ablation of paroxysmal AF. [ABSTRACT FROM AUTHOR]

Investigates the application of ablation of atrial fibrillation (AF) in non-pulmonary vein (PV) foci. Method to identify the atrial ectopic focus; Technique to utilized catheter ablation in non-PV AF; Factor to sconsider upon initiating ablation procedure in patient with heart disease.

Introduction: The outcome of patients with early recurrence of atrial fibrillation (AF) (within one month) after ablation procedure is controversial. Furthermore, the predictors of early and late (up to mean follow-up 30 months) recurrence of AF are not investigated in depth.Aims Of the Study: The aim of the present study was to investigate the predictors of early and late recurrence of AF after catheter ablation of arrhythmogenic foci initiating AF in patients with paroxysmal AF.Methods and Results: The study included 207 patients (155 men; mean age 62 +/- 13 years) who received catheter ablation of paroxysmal AF. Eighty-one (39%) patients had early recurrence of AF. Five clinical variables were related to the early recurrence of AF: (1) old age (>/=65 years) ( P = 0.004); (2) presence of associated cardiovascular disease ( P = 0.01); (3) presence of multiple AF foci ( P = 0.004); (4) presence of AF foci from left atrial free wall ( P = 0.039); (5) left atrial enlargement ( P = 0.038). Multivariate analysis demonstrated that presence of multiple AF foci could predict early recurrence of AF ( P = 0.013; ratio = 2.24; 95% CI 1.18 to 4.25). During the follow-up period (30 +/- 11 months), 70 (34%) patients had late recurrence of AF, and two clinical variables were related to the late recurrence of AF: (1) presence of early recurrence of AF ( P = 0.025); (2) presence of multiple AF foci ( P = 0.034). Multivariate analysis found that presence of early recurrence of AF could predict late recurrence of AF ( P = 0.046; hazard ratio = 1.62; 95% CI 1.01 to 2.59). Late recurrence of AF happened in 35 (43%) of the 81 patients with early recurrence of AF, and in 35 (28%) of the 126 patients without early recurrence of AF.Conclusions: Early AF recurrence could predict late AF recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Acquired pulmonary vein (PV) stenosis is a well-known complication following catheter ablation of atrial fibrillation (AF). However, the details of congenital PV stenosis have not been reported in patients who underwent catheter ablation of AF. Methods and Results: A total of 178 patients (110 men, age: 54 ± 11 years) with drug-refractory AF received MRA or multidetector CT (MDCT) before ablation for delineation of PV morphologies. Five PVs in 5 patients (2.8%) showed at least 50% stenosis before ablation. We demonstrated two types of preexisting PV stenosis. Type I is the external compression of PV by the descending aorta, observed in LIPV of the three patients. Type II is the focal narrowing of PV, observed in RSPV of the two patients. Conclusion: Preexisting stenosis of PV may be a consequence of congenital focal narrowing or external compression by the adjacent structures. Detection of this condition by 3D CT or MRA before catheter ablation can provide information for planning of ablation strategy and prevent misdiagnosis of ablation-related PV stenosis. [ABSTRACT FROM AUTHOR]

Previous studies have reported that increased high-sensitive C-reactive protein (hs-CRP) levels are associated with an inflammatory state. This study investigated the association among hs-CRP, substrate properties, and long-term clinical outcomes after catheter ablation of atrial fibrillation (AF). A total of 137 patients with AF (54 ± 13 years) who underwent mapping and catheter ablation were included. The hs-CRP was measured before the first ablation procedure. The substrate properties (initiating triggers, biatrial mean voltage, and high-frequency sites) of the 2 atria and long-term outcome were investigated in patients in the low hs-CRP group (<75%, 2.92 mg/L) and high hs-CRP group (>75%, 2.92 mg/L). Patients with a higher hs-CRP were associated with an increased number of identified nonpulmonary vein ectopies (34.4% vs 17%, p = 0.034), lower mean left atrial (LA) voltage (1.72 ± 0.73 vs 1.92 ± 0.72 Hz, p = 0.045), and higher-frequency sites in the left atrium (71% vs 37%, p = 0.027). After a median follow-up period of 15 months, the single-procedure success rate (72% vs 53%, p = 0.008) and final success rate after multiple procedures (94% vs 81%, p = 0.02) were higher in the low hs-CRP group. In a multivariable regression model adjusted for other potential covariates, hs-CRP level (p = 0.021) and LA diameter (p = 0.032) were independent predictors of recurrence. In conclusion, baseline CRP levels before the first AF ablation procedure had an independent prognostic value in predicting long-term recurrence. Patients with a high hs-CRP level were associated with an abnormal LA substrate and high incidence of nonpulmonary vein AF sources. [Copyright &y& Elsevier]