Simple and novel technique to confirm complete mitral isthmus block.

BACKGROUND: Differential pacing technique to confirm mitral isthmus (MI) block is sometimes challenging due to destroyed tissues after extensive ablation. The purpose of this study is to set an endpoint of MI ablation using conduction time around the mitral annulus (MA). METHODS: Forty-five consecutive patients with persistent atrial fibrillation who received MI linear ablation were included. The geometry and activation times of the left atrium around the MA were collected using a multipolar catheter before ablation. During coronary sinus (CS) pacing, the time between the stimulus and the wave-front collision at the opposite side of the MA (defined as T/2) was calculated, and the doubled value was defined as the estimated perimitral conduction time (E-PMCT). The endpoint for complete MI block was when the stimulus (at distal CS) minus the maximal delayed potential (St-MDP) on the MI interval reached the E-PMCT. RESULTS: St-MDP reached E-PMCT during MI ablation in 44/45 patients. Among these 44 patients, differential pacing revealed bidirectional block in 39/44 (88.6%), whereas in 5/44 (11.4%), the differential pacing was not possible because of the loss of capture of local potentials due to extensive applications around the linear line. In one patient, the St-MDP did not reach E-PMCT (E-PMCT: 148 ms, St-MDP :130 ms) and differential pacing revealed no MI block. E-PMCT values (median 176 ms) correlated strongly with St-MDP (median 185 ms, P < 0.0001, R = 0.98). CONCLUSIONS: Although E-PMCT differs between individuals, the value is significantly correlated with the St-MDP. This technique may be useful in providing an individual endpoint of MI ablation as an alternative to differential pacing.

Novel Ablation Strategy for Isolating the Superior Vena Cava Using Ultra High-Resolution Mapping.

BACKGROUND: The aim of this study was to categorize the conduction patterns between the right atrium (RA) and the superior vena cava (SVC), and to determine the ideal procedure for SVC isolation using a novel high-resolution mapping system.Methods and Results:RA-SVC conduction was evaluated using the RHYTHMIA system in 113 patients (age 62.8±11.5 years, paroxysmal: 67) with atrial fibrillation (AF) after pulmonary vein (PV) isolation. In 56 patients, a line of conduction block was found to run obliquely just above the sinus node (Block group). The remaining 57 patients did not have block (Non-block group). Non-PV foci were spontaneous or provoked with isoproterenol after electrical cardioversion of pacing-induced AF. In 43 patients with SVC foci (Block group: 22, Non-Block group: 21), SVC was isolated by radiofrequency applications delivered along the line connecting the open ends of the block line (Block group) or by conventional methods (Non-block group). The Block group required fewer radiofrequency deliveries for SVC isolation than the Non-Block group (4.2±0.9 vs. 10.2±2.8 times; P<0.0001). The isolated SVC area was larger in the Block group (15.7±3.7 vs. 10.5±3.1 cm2; P<0.0001). CONCLUSIONS: We found that approximately half of patients with AF had a diagonal line of block at the RA-SVC junction that could be utilized to isolate the SVC with fewer radiofrequency deliveries.

The proportion of asymptomatic recurrence after catheter ablation of atrial fibrillation in patients with a pacemaker for sick sinus syndrome.

BACKGROUND: Catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) is an effective treatment. However, the frequency of asymptomatic AF recurrence after CA in patients with PAF and sick sinus syndrome (SSS) is not clear. The aim of this study was to elucidate the real AF recurrence after CA in patients with PAF and a pacemaker for SSS. METHODS AND RESULTS: Fifty-one consecutive patients (mean age 66.6 ± 7.0 years, male 34) with PAF and SSS and pacemakers underwent CA. All patients were followed at 1, 3, 6, 9, and 12 months after the CA using a 12-lead ECG, Holter-ECG, and 1-month event recorder as a conventional follow-up. In addition, the pacemakers were interrogated every 12 months. During a 5-year follow-up after the final CA procedure, AF recurrences were observed in 7 patients (13.7%) with a conventional follow-up, including 1 (2.0%) asymptomatic patient. Pacemaker-interrogation revealed another 10 patients (19.6%) with asymptomatic AF recurrences. Ultimately, the conventional follow-up plus pacemaker-interrogation provided a higher incidence of AF recurrences (P = 0.009). Multiple CA procedures contributed to a significant increase in the AF-free survival rate at 5 years: 58.6% after a single CA and 86.0% after multiple CA procedures with a conventional follow-up, but which decreased to 40.6% and 60.9% with a conventional follow-up plus a pacemaker interrogation, respectively. CONCLUSIONS: One-third of PAF patients with SSS and pacemakers recurred after multiple CA sessions. However, 65% of them were asymptomatic and difficult to be identified with conventional follow-up. Pacemaker interrogation significantly increased the detection rate of AF-recurrence.

Rapid Mapping of Right Atrial Tachycardia Using a New Multielectrode Basket Catheter.

INTRODUCTION: The mapping of atrial tachycardia (AT) can often be challenging and time-consuming, especially in patients with ATs that develop following cardiac surgery or are concomitant with atrial fibrillation. Recently, a new multielectrode basket catheter (MBC) has become available; we hypothesized that the MBC could be utilized to diagnose AT circuits. METHODS AND RESULTS: This study included 51 consecutive patients undergoing catheter ablation of clinically documented right-sided ATs (including 17 cases following cardiac surgery). Using a NavX system, 2 activation maps of the ATs were created, one using the new MBC (32 mm, 31 poles) and the other using a circular catheter. The time needed to complete the activation maps and the points acquired with both mapping catheters were compared. In all 64 ATs, including 34 non-cavotricuspid isthmus-dependent ATs, the AT activation maps created by both catheters were essentially identical. The number of points acquired to complete the activation maps did not differ significantly between the MBC and the circular catheter (387 [285-511] vs. 374 [269-533], P = 0.19), but the mapping time was significantly shorter using the MBC (4.0 [3.0-6.0] minutes vs. 8.0 [6.5-10.0] minutes, P < 0.0001). Inadvertent mechanical AT termination (n = 6) was observed only during mapping with the circular catheter. CONCLUSION: In patients with right-sided ATs, the use of an MBC could save mapping time.

Apixaban versus Warfarin for the Prevention of Periprocedural Cerebral Thromboembolism in Atrial Fibrillation Ablation: Multicenter Prospective Randomized Study.

INTRODUCTION: Stroke can be a life-threatening complication of atrial fibrillation (AF) catheter ablation. Uninterrupted warfarin treatment contributes to minimizing the risk of stroke complications. METHODS AND RESULTS: This was a prospective, open-label, randomized, multicenter study assessing the safety and efficacy of apixaban for the prevention of cerebral thromboembolism complicating AF catheter ablation. Two hundred patients with drug-resistant AF were equally assigned to take either apixaban (5 mg or 2.5 mg twice daily) or warfarin (target international normalized ratio, 2-3) for at least 1 month before AF ablation. Neither drug regimen was interrupted throughout the operative period. Diffusion-weighted magnetic resonance imaging was performed for all patients to detect silent cerebral infarction (SCI) after the ablation. Primary outcomes were defined as the occurrence of stroke, transient ischemic attack, SCI, or major bleeding that required intervention. The secondary outcome was minor bleeding. The groups did not statistically differ in patients' backgrounds or procedural parameters. During AF ablation, the apixaban group required administration of more heparin to maintain an activated clotting time > 300 seconds than the warfarin group (apixaban, 14,000 ± 4,000 units; warfarin, 9,000 ± 3,000 units). Three primary outcome events occurred in each group (apixaban, 2 SCI and 1 major bleed; warfarin, 3 SCI, P = 1.00), and 3 and 4 secondary outcome events occurred in the apixaban and warfarin groups (P = 0.70), respectively. CONCLUSION: Apixaban has similar safety and effectiveness to warfarin for the prevention of cerebral thromboembolism during the periprocedural period of AF ablation.

Ectopic expression of Ptf1a induces spinal defects, urogenital defects, and anorectal malformations in Danforth's short tail mice.

Danforth's short tail (Sd) is a semidominant mutation on mouse chromosome 2, characterized by spinal defects, urogenital defects, and anorectal malformations. However, the gene responsible for the Sd phenotype was unknown. In this study, we identified the molecular basis of the Sd mutation. By positional cloning, we identified the insertion of an early transposon in the Sd candidate locus approximately 12-kb upstream of Ptf1a. We found that insertion of the transposon caused overexpression of three neighboring genes, Gm13344, Gm13336, and Ptf1a, in Sd mutant embryos and that the Sd phenotype was not caused by disruption of an as-yet-unknown gene in the candidate locus. Using multiple knockout and knock-in mouse models, we demonstrated that misexpression of Ptf1a, but not of Gm13344 or Gm13336, in the notochord, hindgut, cloaca, and mesonephros was sufficient to replicate the Sd phenotype. The ectopic expression of Ptf1a in the caudal embryo resulted in attenuated expression of Cdx2 and its downstream target genes T, Wnt3a, and Cyp26a1; we conclude that this is the molecular basis of the Sd phenotype. Analysis of Sd mutant mice will provide insight into the development of the spinal column, anus, and kidney.

Impact of Non-Pulmonary Vein Foci on the Outcome of the Second Session of Catheter Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Paroxysmal atrial fibrillation (AF) is primarily triggered by pulmonary veins (PVs). However, non-PV AF foci may also trigger AF. METHODS: We examined 207 patients (mean age, 62 ± 11 years; 166 men) who underwent a second catheter ablation (CA) and evaluated the clinical significance of non-PV AF foci on the outcomes. RESULTS: Electrical reconnections between the PVs and left atrium (LA) were observed in 162 patients (78.3%). Non-PV AF foci were identified in 95 patients (45.9%, 60 patients with successfully ablated non-PV AF foci and 35 with unmappable non-PV AF foci). During a median follow-up period of 22.7 months, 61 patients (29.5%; 18/112 [16.1%] without non-PV AF foci vs. 20/60 [33.3%] with successfully ablated non-PV AF foci vs. 23/35 [65.7%] with unmappable non-PV AF foci, P < 0.0001) developed AF recurrence; 52 (85.2%) developed recurrence within 1 year. The presence of non-PV AF foci was a significant clinical predictor of AF recurrence after the second CA; successfully ablated non-PV AF foci increased the AF recurrence risk by 2.24 times (95% confidence interval [CI], 1.12-4.54; P = 0.02), and unmappable AF foci increased this risk by 5.58 times (95% CI, 2.73-11.63; P < 0.0001). CONCLUSION: Nearly half of the patients had non-PV AF foci at the second CA session. AF recurred after the second CA session in approximately 30%, with most recurrences happening within 1 year. The presence of non-PV AF foci significantly increased the AF recurrence risk after a second CA. When non-PV AF foci were unmappable, the AF recurrence rate was extremely high.

Simultaneous isolation of superior and inferior pulmonary veins on both the left and right sides could yield better outcomes in patients with paroxysmal atrial fibrillation.

AIMS: This study investigated whether disappearance patterns of pulmonary vein (PV) potentials (PVPs) during PV isolation (PVI) affect the outcome of catheter ablation (CA) in patients with paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: Extensive PVI was performed in 1149 PAF patients (age, 61 ± 10 years). Clinical and demographic characteristics, ablation data, and follow-up outcomes were prospectively collected. During an initial CA, simultaneous disappearance of superior and inferior PVPs in both right and left PVs was observed in 464 (40.4%) patients (Group S). Atrial fibrillation-recurrence free rates at 1, 3, and 5 years after the initial CA in Group S were 78.9, 71.9, and 68.1%, respectively, which were higher than those in Group Non-S (P = 0.004). However, those were similar after the final CA between both groups. The incidence of PV-left atrium (LA) electrical reconnection was significantly lower in Group S than in Group Non-S in the second (Group S, 65.6% vs. Group Non-S, 82.1%; P = 0.004) and third (Group S, 8.3% vs. Group Non-S, 47.6%; P = 0.03) CAs. Furthermore, the reconnections more frequently occurred on the side of PVs where simultaneous PVP elimination had not been achieved at the initial CA. Simultaneous disappearance of superior and inferior PVPs in both right and left PVs independently reduced the risk of AF recurrence after the initial CA by 26%. CONCLUSIONS: The simultaneous disappearance of superior and inferior PVPs in both right and left PVs is associated with less frequent PV-left atrium reconnection and may yield a better clinical outcome after the initial CA.

The impact of haemodialysis on the outcomes of catheter ablation in patients with paroxysmal atrial fibrillation.

AIMS: The outcomes of catheter ablation (CA) in patients with paroxysmal atrial fibrillation (PAF) who are undergoing haemodialysis (HD) have not been fully elucidated. This study aimed to determine the impact of HD on CA outcome in these patients. METHODS AND RESULTS: We examined 1364 consecutive PAF patients (mean age, 61 ± 10 years) who underwent CA, including 32 (2.3%) patients undergoing HD. The patients undergoing HD had a significantly lower body mass index (P < 0.0001), higher CHADS2 score (P = 0.006), and higher prevalence of structural heart disease (P < 0.0001), hypertension (P = 0.002), and congestive heart failure (P = 0.02). Echocardiography indicated a larger left atrial diameter (P < 0.0001) and left ventricular diameter (P = 0.0002) in the HD patients. Haemodialysis was a significant predictor of AF recurrence (hazard ratio 2.56; 95% confidence interval 1.56-4.03; P = 0.0004) in the overall population. Sinus rhythm maintenance rates in the HD patients at 1, 3, and 5 years were 42.3, 37.6, and 19.7%, respectively, after the first procedure, and 64.7, 54.9, and 47.1%, respectively, after the final procedure (median, 2; range, 1-2 procedures); these rates were significantly lower than those in the non-HD patients (P < 0.0001). The 5-year survival rate was 78.1% in the HD patients. CONCLUSION: Haemodialysis was significantly associated with AF recurrence after CA for PAF. However, an ∼50% success rate for sinus rhythm maintenance without antiarrhythmic drug therapy in HD patients suggested that CA could be an option for the treatment of AF.

Oesophageal cooling with ice water does not reduce the incidence of oesophageal lesions complicating catheter ablation of atrial fibrillation: randomized controlled study.

AIM: Atrial fibrillation (AF) ablation can result in oesophageal injuries that lead to atrio-oesophageal fistulae, a life-threatening complication. This study aimed to evaluate whether oesophageal cooling could prevent oesophageal lesions complicating AF ablation. METHODS AND RESULTS: We randomly assigned 100 patients with drug-resistant AF to an oesophageal cooling group or a control group. In the oesophageal cooling group, we injected 5 mL of ice water into the oesophagus prior to radiofrequency (RF) energy delivery adjacent to the oesophagus. If the oesophageal temperature reached 42°C, the RF energy delivery was stopped, and the ice water injection was repeated. In the control group, oesophageal cooling was not applied. Oesophageal endoscopy was performed 1 day after the catheter ablation, and lesions were qualitatively assessed as mild, moderate, or severe. The numbers of ablation sites with an oesophageal temperature of >42°C were 1.7 ± 1.4 and 2.6 ± 1.7 in the oesophageal cooling group and the control group, respectively (P = 0.04), and the maximal oesophageal temperature at those sites was 43.0 ± 0.6 and 44.7 ± 0.9°C (P < 0.0001). Oesophageal lesions occurred almost equally between the oesophageal cooling group [10 of 50 patients (20%)] and the control group [11 of 50 patients (22%)]. However, the severity of the oesophageal lesions was slightly milder in the oesophageal cooling group (three moderate, seven mild) than in the control group (three severe, one moderate, seven mild). CONCLUSION: Oesophageal cooling may alleviate the severity of oesophageal lesions but does not reduce the incidence of this complication under the specific protocol evaluated here.

Late-phase thromboembolism after catheter ablation for paroxysmal atrial fibrillation.

BACKGROUND: The aim of this study was to investigate the incidence and predictors (which have not previously been fully elucidated) of late-phase thromboembolism (TE) after catheter ablation (CA) for paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: We studied 1,156 consecutive patients (61±10 years; 891 men; CHADS2score, 0.8±1.0) after CA for symptomatic paroxysmal AF and examined the details of late-phase TE. During a follow-up of 49.5±21.9 months (median, 47 months; range, 6-113 months) after CA, 9 patients (0.78%) developed late-phase TE, all of which were ischemic stroke. Of these, 5 patients with AF recurrence experienced cardioembolism; the AF was asymptomatic at recurrence. The remaining 4 without AF recurrence experienced cardioembolism (n=1), small-vessel occlusion (n=1), large-artery atherosclerosis (n=1), and stroke of other determined etiology (n=1). On Kaplan-Meier analysis patients with structural heart disease (P=0.003), AF recurrence after the final CA (P=0.01), prior stroke (P=0.002), CHADS2score ≥2 (P=0.0002), left ventricular ejection fraction <50% (P<0.0001), and spontaneous echo contrast on transesophageal echocardiogram (P=0.0004) had a significantly higher risk of late-phase TE. Multivariate analysis indicated that CHADS2score ≥2 (HR, 4.49; 95% CI: 1.08-22.56; P=0.04) independently predicted late-phase TE. CONCLUSIONS: The incidence of TE was low after CA for paroxysmal AF, but CHADS2score ≥2 independently increased the risk of late-phase TE.

Differential Pacing Maneuver From the Vein of Marshall.

BACKGROUND: Bidirectional mitral isthmus (MI) block is conventionally verified by differential pacing from the coronary sinus (CS) and its sequence change. This study aimed to evaluate the ability of differential pacing from the vein of Marshall (VOM) to detect epicardial MI connections. METHODS: Radiofrequency and VOM ethanol MI ablation were performed with a VOM electrode catheter inserted to the septal side of the ablation line. MI block was verified using conventional CS pacing. To perform differential VOM pacing analysis, initial pacing was delivered from a distal VOM bipole closer to the block line, and then from a proximal VOM bipole. The intervals from pacing stimulus during different VOM pacing sites to the electrogram recorded through the CS catheter on the opposite side of the line were compared. When the interval during distal VOM pacing was longer than that during proximal VOM pacing, it indicated a VOM connection block; however, if the former interval was shorter, the connection through the VOM was considered persistent. RESULTS: Overall, 50 patients were evaluated. According to CS pacing, MI ablation was incomplete in 9 patients, in whom the analysis indicated persistent VOM connection. Among 41 patients with complete MI block, confirmed by CS finding, in 30 (73%) patients, the interval during distal VOM pacing was longer than that during proximal VOM pacing by 11±5 ms. However, in 11 patients (27%) the former interval was revealed to be shorter than the latter by 16±8 ms, indicating residual VOM connection. Conduction time across the line was significantly shorter in 11 patients than in the other 30 (166±21 versus 197±36 ms; P<0.01). Ten successful reevaluated analyses after VOM ethanol and further radiofrequency ablation of the connection indicated VOM block achievement. CONCLUSIONS: Differential VOM pacing maneuver reflects the VOM conduction status. This maneuver can uncover residual epicardial connections that are missing with CS pacing.

Prevention of periprocedural ischemic stroke and management of hemorrhagic complications in atrial fibrillation ablation under continuous warfarin administration.

INTRODUCTION: This study aimed to determine the effects of continuing warfarin administration during the periprocedural period of catheter ablation for atrial fibrillation (AF) on the prevention of stroke complications and to evaluate the management of hemorrhagic complications occurring with this approach. METHODS AND RESULTS: A total of 3,280 patients undergoing AF catheter ablation at our institution were divided into 2 groups: the first 1,953 patients who discontinued warfarin 3-4 days before AF ablation and were bridged with heparin (warfarin-discontinued group), and the last 1,327 patients who continued warfarin throughout the periprocedural period (warfarin-continued group). Symptomatic stroke or transient ischemic attack occurred in 13/1,953 patients (0.67%) in the warfarin-discontinued group and in 2/1,327 patients (0.15%) in the warfarin-continued group (P = 0.021). None of the patients with therapeutic international normalized ratio at the time of the procedure had periprocedural thromboembolism in the warfarin-continued group. Major hemorrhagic complications occurred in 26/1,953 patients in the warfarin-discontinued group (1.3%; 25 with cardiac tamponade and 1 with retroperitoneal bleeding), and in 15/1,327 patients in the warfarin-continued group (1.1%; 14 with cardiac tamponade and 1 with abdominal wall bleeding) (P = 0.80). Of the 14 warfarin-continued patients with cardiac tamponade, 13 were administered prothrombin complex concentrate (PCC) and vitamin K; the bleeding was stopped safely without surgical repair. CONCLUSION: The continuation of warfarin during the periprocedural period of AF ablation could reduce the incidence of stroke without increasing hemorrhagic complications. When cardiac tamponade occurred with this approach, it was safely treated with PCC and vitamin K.

Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases.

INTRODUCTION: This study aimed to elucidate the clinical characteristics and management of periesophageal vagal nerve injury complicating the ablation of atrial fibrillation (AF). METHODS AND RESULTS: A total of 3,695 patients with drug-resistant AF underwent extensive pulmonary vein isolation at our institution. Either a nonirrigated or an irrigated ablation catheter was employed, with radiofrequency power of 25-40 W. Esophageal temperature was monitored in 3,538 patients: when the esophageal temperature reached 42°C radiofrequency delivery was stopped. A total of 11 patients (60 ± 11 years, 10 males) were diagnosed as having a periesophageal vagal nerve injury after the AF ablation. Symptoms included nausea, vomiting, bloating, constipation, and gastric pain, which occurred within 72 hours after the procedure. Gastrointestinal fluoroscopy and/or endoscopy revealed gastric hypomotility (10 patients) and pyloric spasm (1 patient). Intravenous erythromycin (3 mg/kg every 8 hours) was effective in relieving symptoms in 5 patients, and the patient with pyloric spasm underwent esophagojejunal anstomosis. Eight patients almost fully recovered within 40 days; however, 3 patients suffered from severe symptoms for 3-12 months. This complication occurred in 4 of the 157 patients (2.5%) who did not have esophageal temperature monitoring, and 7 of the 3,538 (0.2%) who did (P = 0.0007). The 3 patients with persistent severe symptoms received no esophageal temperature monitoring. CONCLUSION: The clinical course and severity of the periesophageal vagal nerve injury varied, but most patients finally recovered with conservative treatment. Radiofrequency delivery under esophageal temperature monitoring might reduce both the incidence and the severity of this complication.

Renal function after catheter ablation of atrial fibrillation.

BACKGROUND: Kidney function is a known predictor of cardiovascular morbidity and mortality. Although patients with atrial fibrillation (AF) often have kidney dysfunction, less is known about the association between AF and kidney function. We sought to assess changes in kidney function after catheter ablation of AF. METHODS AND RESULTS: Patients who underwent catheter ablation of AF were recruited for the present prospective study. Estimated glomerular filtration rate (eGFR) was evaluated before and 1 year after the ablation. Three hundred eighty-six patients (paroxysmal AF, 135; persistent AF, 106; longstanding persistent AF, 145) were studied. Their baseline eGFR was 68 ± 14 mL · min(-1) · 1.73 m(-2). Sixty-six percent and 26% of patients had eGFR of 60 to 89 and 30 to 59 mL · min(-1) · 1.73 m(-2), respectively. Overall, 278 patients (72%) were arrhythmia free over a 1-year follow-up. In patients free from arrhythmia, eGFR increased 3 months later and was maintained until 1 year, whereas in patients with recurrences, eGFR had decreased over 1 year. Changes in eGFR over 1 year in patients free from arrhythmia differed significantly compared with those with recurrences (3 ± 8 versus -2 ± 8 mL · min(-1) · 1.73 m(-2); P<0.0001). In all quartiles of baseline eGFR, changes in eGFR over 1 year after the ablation were greater in patients free from arrhythmia compared with those with recurrences. CONCLUSION: Elimination of AF by catheter ablation was associated with improvement of kidney function over a 1-year follow-up in patients with mild to moderate kidney dysfunction.

Intuitive diagnosis of complex atrial tachycardia mechanisms using a novel histogram module of an ultra-high-resolution mapping system.

PURPOSE: The LUMIPOINT™ software module was developed to aid the physician in determining the mechanism of individual atrial tachycardias (ATs). The purpose of this study was to assess the clinical utility of the SKYLINE™ histogram that is a part of LUMIPOINT™. METHODS: This study included consecutive patients with iatrogenic sustained AT who underwent catheter ablation using conventional mapping (RHYTHMIA™). SKYLINE™ patterns were analyzed offline and classified into two types: (1) focal type (type-F) exhibiting a low-amplitude (relative activating surface area < 10%) plateau period and (2) reentrant type (type-R) showing no plateau period. How well the two patterns distinguished between focal and macroreentrant ATs as determined by conventional mapping was evaluated. RESULTS: We studied 101 iatrogenic ATs in 91 patients (female: 24, mean age: 67.3 ± 9.1 years). Activation mapping revealed 79 (78.2%) macroreentrant, 6 (5.9%) localized reentrant, and 16 (15.8%) focal ATs. Among the 72 type-R ATs, the mechanism was truly a macroreentry in 70 ATs. However, one focal AT and one localized reentrant AT displayed a type-R pattern (pseudo-reentry pattern). In the 29 type-F ATs, nine macroreentrant ATs were recognized (pseudo-focal pattern). Using SKYLINE™ type-R to differentiate macroreentrant AT from AT with centrifugal activation (focal or localized reentry), the sensitivity and specificity were 88.6% and 90.9%, respectively. Even when the SKYLINE™ type did not match the mapping-based AT mechanism, all discrepancies were electrophysiologically explicable using the SKYLINE™ histograms. CONCLUSIONS: SKYLINE™ histograms are a useful tool for the intuitive diagnosis of AT mechanisms.

Effect of radiofrequency and ethanol ablation on epicardial conduction through the vein of Marshall: How to detect and manage epicardial connection across the mitral isthmus.

BACKGROUND: The vein of Marshall (VOM), which is surrounded by the Marshall bundle (MB), behaves as an epicardial connection bypassing the mitral isthmus. The influence of radiofrequency ablation and VOM ethanol infusion (VOM-EI) on epicardial MB conduction remains unclear. OBJECTIVE: The purpose of this study was to evaluate MB conduction status during mitral isthmus ablation. METHODS: Of 57 consecutive patients undergoing mitral isthmus ablation, 50 with electrode catheter cannulation into the VOM were analyzed. MB conduction was investigated by evaluating electrograms inside the VOM. Endocardial ablation was initially performed, followed by ablation inside the coronary sinus (CS), if required. Selective VOM-EI was performed if the MB potentials still exhibited early activation after radiofrequency ablation, suggesting the presence of MB connection bridging the mitral isthmus. RESULTS: VOM electrograms composed of near-field MB and far-field left atrial potentials were recorded in all patients. Solely with endocardial ablation, 33 patients (66%) achieved entire mitral isthmus block, and 43 patients (86%) achieved an epicardial MB conduction block. MB potentials exhibited early activation in the remaining 7 (14%), even after requiring CS ablation. VOM-EI then was performed. Elimination of MB potentials was verified by electrode catheter reinsertion after VOM-EI. Mitral isthmus conduction was successfully blocked during VOM-EI in 4 patients and during additional radiofrequency ablation in the remaining 3. All patients finally achieved entire mitral isthmus block. CONCLUSION: MB is effectively ablated by radiofrequency ablation. Continuous evaluation of MB conduction can reveal epicardial conduction and ablation effect. A residual MB epicardial connection is relatively rare but can be ablated by VOM-EI.

Germinal center-associated nuclear protein (GANP) is involved in mRNA export of Shugoshin-1 required for centromere cohesion and in sister-chromatid exchange.

Germinal center-associated nuclear protein (GANP) is a 210-kDa protein that is upregulated in rapidly proliferating B cells. GANP contains regions for RNA-primase and minichromosome maintenance 3 (MCM3)-associated activities, as well as a Sac3-homology region, which is associated with mRNA export in yeast. Here, we examined the role of GANP in mRNA export and cell proliferation in mammalian cells. The ganp small interfering RNA (siRNA) induced cell-cycle arrest at the G2/M-phase, but increased abnormal chromosome alignment of metaphase chromosomes and cell apoptosis in HeLa cells. These changes were not associated with either the abnormality of the spindle assembly checkpoint or the expression level of cohesin. ganp siRNA disrupted the assembly and localization of cohesin at the centromeres in metaphase cells, which is a quite similar phenotype caused by Shugoshin-1 (Sgo1) siRNA-treatment, which was reported previously. ganp siRNA did induce a selective decrease in Sgo1 transcript levels in the cytoplasm, resulting in a lack of cohesin at the centromeres in metaphase and premature separation of the sister chromatids at mitosis. GANP lacking the Sac3-homology region caused the dominant-negative effect with similar abnormalities and impaired mRNA export. Thus, human GANP is critically involved in cell proliferation at the mitotic phase through its selective support of Sgo1 mRNA export.

Expression and localization of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in murine and human placentas.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is one of the scavenger receptors that recognizes oxidized low-density lipoprotein as a major ligand. The placenta is a major source of prooxidant during pregnancy, and the level of placental oxidative stress increases rapidly at the end of the first trimester and tapers off later in gestation. In our study, we evaluated placental expression of LOX-1 during different gestational stages in mice and humans. We used immunohistochemistry and ISH to identify LOX-1-expressing cells in murine and human placentas. In both species, higher expression of LOX-1 mRNA during early to midgestational stages compared with late gestation-corresponding to the increased oxidative stress in early pregnancy-was shown by real-time RT-PCR. In murine placenta, we showed that LOX-1-expressing cells were fibroblast-like stromal cells in metrial glands and decidua basalis and that they were glycogen trophoblast cells in the junctional and labyrinth zones. In the human, LOX-1 expression was detected in villous cytotrophoblasts in both first trimester and term placentas. These localization patterns of LOX-1 in murine and human placentas suggest the possible involvement of LOX-1 in high oxidative stress conditions of pregnancy.

Agonistic and antagonistic effects of C5a-chimera bearing S19 ribosomal protein tail portion on the C5a receptor of monocytes and neutrophils, respectively.

C-terminus of S19 ribosomal protein (RP S19) endows the cross-linked homodimer with a dual effect on the C5a receptor in leucocyte chemoattraction; agonistic effect on the monocyte receptor, and antagonistic effect on the neutrophil receptor. C5a exhibits the uniform agonistic effect on this receptor of both cell types. We have currently prepared a recombinant C5a-chimeric protein bearing the C-terminus of RP S19 (C5a/RP S19 chimera) to be used as a substitute of the RP S19 dimer. In vitro, this chimera similarly inhibited the intracellular Ca(2+) mobilization of neutrophils induced by C5a to the RP S19 dimer did. In the guinea pig skin, 10(-7) M C5a/RP S19 chimera exhibited an inhibitory capacity to the neutrophil infiltration induced by 3 x 10(-7) M C5a without enhancing monocyte infiltration. In reverse passive Arthus reaction, the neutrophil infiltration associated with plasma extravasation was significantly reduced by the simultaneous administration of 10(-7) M C5a/RP S19 chimera with antibodies. The C5a/RP S19 chimera is a useful tool not only to examine the molecular mechanism that underlies the functional difference of the C5a receptor between monocytes and neutrophils, but also to prevent C5a-mediated hyper-response of neutrophils in acute inflammation.