Toshiya Kurotobi

Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation : Role of nitric oxide

BACKGROUND Platelet activation and decreased levels of nitrite and nitrate (NOx), stable end products of nitric oxide (NO), are reported in patients with atrial fibrillation (AF). We examined the time-course changes in plasma NOx levels and the expression of P-selectin on platelets after the onset of AF in a canine model and determined whether these parameters could be risk factors for silent cerebral infarction in patients with AF. METHODS AND RESULTS AF was induced by rapid atrial pacing in the canine model of AF. Plasma NOx levels were significantly decreased and the levels of P-selectin on platelets and of neutrophil/platelet conjugates were significantly increased after the onset of AF in this model. The in vitro experiments demonstrated that the inhibition of NO synthesis increased the expression of P-selectin on platelets. Plasma NOx levels (19.7+/-2.4 versus 27.5+/-2.8 micromol/L) were significantly lower in 25 patients with AF compared with age- (+/-2 years) and sex-matched control subjects. Conversely, the levels of P-selectin on platelets (7.6+/-0.8% versus 4.8+/-0.7%) and of neutrophil/platelet conjugates (14.8+/-0.9% versus 8.1+/-0.6%) were significantly higher in patients with AF. Multiple regression analysis revealed that increased P-selectin on platelets and advanced age were associated with the number of foci of silent cerebral infarction. CONCLUSIONS An irregular heart rate that is characteristic of AF appeared to blunt NO synthesis. The increased expression of P-selectin on platelets associated with the reduced NO levels was a risk factor for silent cerebral infarction in patients with AF.

Marshall vein as arrhythmogenic source in patients with atrial fibrillation : Correlation between its anatomy and electrophysiological findings

Background: Atrial fibrillation (AF) may originate from catecholamine‐sensitive vein of Marshall (VOM) or its ligament in addition to pulmonary veins (PVs). The anatomy of VOM and its relation to arrhythmogenic foci in the left atrium are unknown. We studied the anatomy of VOM and its relation to foci in patients with AF.

Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial.

AIMS Most of recurrent atrial tachyarrhythmias after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are due to reconnection of PVs. The aim of the present study was to evaluate whether elimination of adenosine triphosphate (ATP)-induced dormant PV conduction by additional energy applications during the first ablation procedure could reduce the incidence of recurrent atrial tachyarrhythmias. METHODS AND RESULTS We randomly assigned 2113 patients with paroxysmal, persistent, or long-lasting AF to either ATP-guided PVI (1112 patients) or conventional PVI (1001 patients). The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of Vaughan Williams class I or III antiarrhythmic drugs at 1 year with the blanking period of 90 days post ablation. Among patients assigned to ATP-guided PVI, 0.4 mg/kg body weight of ATP provoked dormant PV conduction in 307 patients (27.6%). Additional radiofrequency energy applications successfully eliminated dormant conduction in 302 patients (98.4%). At 1 year, 68.7% of patients in the ATP-guided PVI group and 67.1% of patients in the conventional PVI group were free from the primary endpoint, with no significant difference (adjusted hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.74-1.09; P = 0.25). The results were consistent across all the prespecified subgroups. Also, there was no significant difference in the 1-year event-free rates from repeat ablation for any atrial tachyarrhythmia between the groups (adjusted HR 0.83; 95% CI 0.65-1.08; P = 0.16). CONCLUSION In the catheter ablation for AF, we found no significant reduction in the 1-year incidence of recurrent atrial tachyarrhythmias by ATP-guided PVI compared with conventional PVI.

Clinical Implications of Distal Embolization During Coronary Interventional Procedures in Patients With Acute Myocardial Infarction: Quantitative Study With Doppler Guidewire

OBJECTIVES This study sought to investigate the timing and amount of embolic particles generation during the percutaneous coronary intervention (PCI) procedure and studied the relationship between embolic burden and coronary blood flow and myocardial damage. BACKGROUND Distal embolization is a major complication of PCI. The Doppler guidewire (DGW) can detect the embolic particles as high-intensity transient signals (HITS) during the PCI procedure. METHODS We prospectively studied 37 patients with acute myocardial infarction (MI). Under monitoring with the DGW, we performed first and second balloon angioplasty, followed by stenting and post-high-pressure dilatation. Left ventricular ejection fraction (LVEF) (%) and regional wall motion (RWM) (standard deviation/chord) were measured on days 1 and 22. RESULTS The HITS were detected in 35 of 37 patients. The number of HITS was the greatest after stenting (16 +/- 18) followed by first balloon inflation (5 +/- 4). There was a significant correlation between the total number of HITS and the corrected Thrombolysis In Myocardial Infarction frame count (r = 0.52, p = 0.003) and a significant weak inverse correlation between the total number of HITS and changes in LVEF and RWM (r = 0.37, p = 0.03 and r = 0.35, p = 0.04, respectively). CONCLUSIONS Distal embolization is common during PCI in patients with acute MI, and the majority of HITS were observed after stenting. An increase in the total number of HITS is associated with reduced coronary blood flow, and is weakly associated with poor recovery of left ventricular function.

Trigger-Based Mechanism of the Persistence of Atrial Fibrillation and Its Impact on the Efficacy of Catheter Ablation

Background— We investigated the possibility that a frequent trigger action might play a role in the development of persistent atrial fibrillation (PeAF) and the presence of a substrate. Methods and Results— In 263 consecutive patients who underwent catheter ablation (CA) for PeAF, electric cardioversion was performed at the beginning of the procedure to determine the presence or absence of an immediate recurrence of AF (IRAF). We defined an IRAF as a reproducible AF recurrence within 90 s after restoration of sinus rhythm by electric cardioversion. We performed a mean±SD of 1.3±0.5 sessions of CA, including pulmonary vein isolation and ablation of the premature atrial contractions that triggered the IRAF (IRAF triggers), and observed the patients for 17 (10–27) months. An IRAF was observed in 70 patients (27%), but we could not ablate the IRAF triggers in 16 (23%) of these IRAF patients. The recurrence rate of PeAF was higher in patients with an unsuccessful IRAF trigger ablation than in those with successful IRAF trigger ablation (63% versus 11%; P<0.001). A multivariable analysis also revealed that an unsuccessful IRAF trigger ablation was 1 of the independent predictors of recurrent PeAF (odds ratio, 10.9; 95% CI, 3.4–36.7). Conclusions— In the PeAF patients with an IRAF, successful elimination of the IRAF triggers, in addition to pulmonary vein isolation, resulted in a successful CA. These results imply that such triggers play a major role in the AF persistence in these PeAF patients.

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

Background—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. Methods and Results—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 &mgr;g/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). Conclusions—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.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial

AIMS Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. METHODS AND RESULTS A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). CONCLUSION Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase.

Variation during the week in the incidence of acute myocardial infarction: increased risk for Japanese women on Saturdays

Background: Variations in the incidence of acute myocardial infarction during the week may differ between and within communities, according to lifestyle. Objective: To identify potential triggering factors for acute myocardial infarction by examining variations in incidence in the days of the week within the Osaka area of Japan. Patients: Of 2511 consecutive patients in this region who were admitted to hospital for acute myocardial infarction between April 1998 and March 2001 and consented to take part, 2400 who had a definitely identified time of onset were enrolled. Results: For this group as a whole, no significant difference in incidence was noted between days of the week. However, in subgroup analyses women were shown to have significant variation through the week, peaking on Saturday with a 39% increase in relative risk (p = 0.037); working subjects showed a peak on Monday, with a 26% increase in relative risk (p = 0.038). Stratified analyses showed that in working men there was a prominent Monday peak in the onset of infarction, with a 30% increase in relative risk (p = 0.022), while in working women, there was no significant variation through the week. Conclusions: Earlier findings of a Monday peak linked to increased physical and mental occupational stress are confirmed. There is also an increase in uncertain risk factors on Saturdays for Japanese women, possibly involving a stressful weekend burden for women. Confirmation of this finding in other communities may help identify triggers of acute myocardial infarction and be useful in prevention.

Transcollateral retrograde approach with rendezvous technique for recanalization of chronically occluded tibial arteries.

Purpose To describe a novel technique using an antegrade wire in a retrograde microcatheter advanced through a transcollateral vessel for recanalization of challenging infrapopliteal chronic total occlusions. Technique A 75-year-old diabetic man presented with critical limb ischemia manifested as nonhealing ulcers on the toes. Baseline angiography revealed a blunt, long, total occlusion of the anterior tibial artery. A retrograde microcatheter was advanced over a guidewire tracking the collateral channel from the planter artery. Antegrade and retrograde microcatheters were aligned inside the occluded lesion. An antegrade wire was then advanced further down through the retrograde microcatheter. Final angiography of the anterior tibial artery following balloon dilation demonstrated a satisfactory result, without evidence of significant residual stenoses or flow-limiting dissections. Complete wound healing was achieved at 3 weeks. Conclusion This alternative wire method may be useful when traditional interventional approaches are unfeasible.

The significance of the shape of the left atrial roof as a novel index for determining the electrophysiological and structural characteristics in patients with atrial fibrillation.

AIM The silhouette of the left atrial (LA) roof is characterized by the pulmonary veins (PVs) and left atrium, and may include the characteristics of the PV/left atrium arrhythmogenicity in patients with atrial fibrillation (AF). In this study, we examined the hypothesis that the characteristics of the LA roof could help us understand the electrophysiological information of the PVs/left atrium. METHODS AND RESULTS The study population consisted of 153 consecutive patients with AF. The shape of the LA roof was determined by simultaneous right- and left-pulmonary angiography and 64-slice multi-detector-row computed tomography. The silhouette was classified into a deep-V shape (A; n= 35), shallow-V (B; n= 76) shape, and flat or coved shape (C; n= 42) according to the PV/left atrium dominancy. The AF triggers from the PVs (A: 70% vs. B: 57% vs. C: 40%; P= 0.003) became significantly less and those from non-PV sites (A: 6% vs. B: 13% vs. C: 22%; P= 0.043) significantly greater, as the LA shape became flat. Burst-inducible atrial tachyarrhythmias after PV isolation (A: 51% vs. B: 65% vs. C: 79%; P= 0.001) and at the end of the catheter ablation (A: 12% vs. B: 24% vs. C: 36%, P= 0.016) significantly increased, as the LA roof shape became flat. Although the PV diameters did not differ among the three groups, the LA volume (A: 69.5 ± 24.1 vs. B: 85.2 ± 34.9 vs. C: 105.7 ± 45.4 mL; P< 0.001) significantly increased as the LA shape became flat. CONCLUSIONS The shape of the LA roof allowed us to understand the structural and the electrophysiological information of the PVs/left atrium.