The incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation: comparison of warfarin and dabigatran.

BACKGROUND: Cerebral microthromboembolism after atrial fibrillation (AF) ablation has been reported in 4-20% with perioperative warfarin. Dabigatran is a new anticoagulant in patients with nonvalvular AF. We investigated the incidence of asymptomatic cerebral microthromboembolism after AF ablation with perioperative warfarin or dabigatran using diffusion-weighted and T2-weighted magnetic resonance imaging (MRI). METHODS AND RESULTS: Our study included 210 consecutive patients with AF (111 paroxysmal and 99 persistent) who underwent complex fractionated atrial electrogram-guided ablation (combined with pulmonary vein isolation, n = 110). Catheter irrigation was performed in all cases. Uninterrupted warfarin therapy was used in 180 patients (warfarin group) and interrupted only on the morning of the procedure with dabigatran in 30 (dabigatran group). All patients underwent cerebral MRI the day after ablation. New microthromboemboli were detected in 10.0% of the warfarin group and 26.7% of the dabigatran group (P < 0.05). The incidence of hemopericardium treated with pericardiocentesis was lower in the warfarin group than in the dabigatran group (2.5% vs 11.1%, P < 0.05). In multivariate analysis, the use of cardioversion was a predictor of new microthromboembolism development after AF ablation. CONCLUSIONS: The incidence of asymptomatic cerebral microthromboembolism and hemopericardium after AF ablation was significantly lower with perioperative warfarin therapy than with dabigatran therapy. Dabigatran may not be an effective alternative to warfarin for AF ablation, especially in patients who undergo cardioversion.

Atrial fibrillation-induced endothelial dysfunction improves after restoration of sinus rhythm.

BACKGROUND: Recent evidence suggests that atrial fibrillation (AF) adversely affects endothelial function. The goal of this study was to assess endothelial function in patients with AF before and after restoration of sinus rhythm by catheter ablation (ABL). METHODS: Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were conducted with Endo-PAT2000 (Itamar Medical, Caesarea, Israel) in 27 patients with persistent AF before ABL and in 21 control subjects with sinus rhythm (SR). According to cardiac rhythm on the morning after ABL, patients were divided into two groups: day 1-restored SR group (n=19) and day 1-recurred AF group (n=8). Based on the cardiac rhythm at 6 months after ABL, the restored SR group was further subdivided into the month 6-maintained SR group (n=11) and the month 6-recurred AF group (n=6). RESULTS: Loge RH-PAT index (RHI) was significantly lower in the persistent AF group than in the control (SR) group (0.52 ± 0.20; 0.69 ± 0.24, p<0.01). Multivariate logistic regression analysis revealed that persistent AF was the only independent predictor of impaired endothelial function defined as loge RHI<0.6 (odds ratio, 4.96; 95% CI, 1.2 to 21.3; p<0.05). Loge RHI was significantly higher after ABL than before ABL (0.53±0.20; 0.73 ± 0.25; p<0.01) in the day 1-restored SR group. Loge RHI of the month 6-maintained SR group was comparable to that of the day 1-restored SR group. CONCLUSIONS: These results suggest that AF is associated with impairment of endothelial dysfunction and that this impairment is reversed by restoration of sinus rhythm.

Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol.

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.

Effectiveness of esophagus detection by three-dimensional electroanatomical mapping to avoid esophageal injury during ablation of atrial fibrillation.

AIMS: Esophageal-left atrial (LA) fistula during atrial fibrillation (AF) ablation is a fatal event. We explored the relation of the esophagus-to-ablated point distance and esophageal temperature rise. METHODS: Consecutive patients (n=106) underwent complex fractionated atrial electrogram-guided AF ablation using CartoMerge; the pulmonary veins were isolated in 23 patients. Maximum radiofrequency (RF) power near the esophagus was 15 W. Ablated points with esophageal temperature rise (monitored with a probe) to ≥38.0°C were tagged; if ≥39.0°C, RF was discontinued. RESULTS: Of 1647 ablated points near the esophagus, 274 were associated with a temperature rise to 38.0-38.9°C and 241 points to ≥39.0°C. Distances (mm) from points to esophagus were 5.1 ± 0.6 (no rise), 4.2±3.1 (38.0-38.9°C), 2.9 ± 2.5 (≥39.0°C). Altogether, 15.5% of points in the upper LA posterior wall, 41.5% in the middle, and 30.2% in the lower caused rises to ≥38.0°C; 8.7%, 24.6%, and 11.0% caused rises to ≥39.0°C. The middle wall was most affected (p<0.01), as shown by multiple logistic regression analysis (both temperatures). Points causing a rise increased significantly as distance decreased (p<0.001). The odds ratio for rise to ≥38.0°C compared with <4.0 to >5.0 mm distance was 2.28 (p=0.004). The longest distance for ≥38.0°C rise was 18.5 mm. CONCLUSION: Distance is an important predictor of esophageal temperature rise. The middle LA posterior wall is most vulnerable. A dose of 15 W is too high for ablation, especially <4.0 mm from the esophagus. Points >20.0 mm away are relatively safe.

Incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation guided by complex fractionated atrial electrogram.

BACKGROUND: The incidence of cerebral thromboembolism after pulmonary vein isolation (PVI) ranges from 2% to 14%. This study investigated the incidence of cerebral thromboembolism after complex fractionated atrial electrogram (CFAE) ablation with or without PVI. METHODS: One hundred consecutive atrial fibrillation (AF) patients (50 paroxysmal and 50 persistent, including 10 longstanding) who underwent CFAE ablation combined with (n = 41, PVI+CFAE group) or without (n = 59, CFAE group) PVI were studied. Coronary angiography (CAG) was conducted with AF ablation in 5 cases in which coronary artery stenosis was suspected on 3D-computed tomography. PVI was performed before CFAE ablation without circular catheter during AF. After termination of AF, additional ablation was performed to complete PVI with a circular catheter. All patients underwent cerebral magnetic resonance imaging (MRI) including diffusion-weighted MRI and T2-weighted MRI the day after ablation. RESULTS: New thromboembolism was detected in 7.0%, and there was no significant difference between the 2 strategies (7.3% in PVI+CFAE group, 6.8% in CFAE group). CHADS2 score (1.6 ± 1.0 vs 0.8 ± 0.9, P < 0.05), left atrial volume (LAV; 83.8 ± 27.1 vs 67.8 ± 21.8, P < 0.05), and left ventricular ejection fraction (LVEF, 53.1 ± 9.2 vs 65.1 ± 9.7, P < 0.01) were significantly different when comparing patients with or without thromboembolism. In multivariate analysis, LVEF (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.84-0.99; P < 0.05) and concomitant CAG (OR 18.82; 95% CI, 1.77-200.00; P < 0.05) were important predictors of new cerebral thromboembolism. CONCLUSIONS: The incidence of cerebral microthromboembolism after CFAE ablation was not greater than previous reports in PVI. Cautious management is required during AF ablation, especially in the patients with low LVEF.

Relationship between clinical outcomes and unintentional pulmonary vein isolation during substrate ablation of atrial fibrillation guided solely by complex fractionated atrial electrogram mapping.

BACKGROUND: Controversy exists as to whether atrial fibrillation (AF) ablation guided solely by complex fractionated atrial electrogram (CFAE) has a good outcome despite not requiring pulmonary vein isolation (PVI). OBJECTIVES: The purpose of this study was to evaluate the effectiveness of AF ablation guided solely by targeting CFAE areas, and to determine whether its clinical efficacy has any relationship with unintentionally isolating the PV. METHODS: We studied 100 consecutive patients (ages 59 ± 11 years; 54 with paroxysmal, 35 persistent, and 11 long-standing persistent AF), who underwent CFAE-ablation. PV potential (PVP) was recorded before and after ablation. After excluding 39 patients in whom sinus rhythm could not be maintained before ablation by internal cardioversion and/or who had a history of PVI(s), PVPs were analyzed. RESULTS: AF was terminated during ablation in 98% of paroxysmal, 80% of persistent, and 55% of long-standing persistent AF patients. Nifekalant (0.3-0.6 mg/kg) was administered in 30%, 57%, and 83%, respectively. The common areas of CFAE around the PVs were anterior to the right PVs, posterior to the left PVs, and at the ridge of the left atrial appendage. Among 215 PVs in 61 patients (42 paroxysmal, 19 persistent), only 17 PVs (8%) were unintentionally isolated. The atrial potential to PVP was prolonged (>30 ms) in 13% of PVs. After at least 12 months of follow-up (23 ± 5 months), 65% of paroxysmal (11% with drug), 54% of persistent (37% with drug), and 45% of long-standing (60% with drug) AF patients were free from atrial arrhythmia after one session. CONCLUSIONS: CFAE-ablation terminates AF without isolating PVs in a high percentage of patients, and yields excellent clinical outcomes.

Relationship between bilirubin concentration, coronary endothelial function, and inflammatory stress in overweight patients.

AIM: Bilirubin has antioxidant properties and may protect against atherosclerosis and coronary heart disease (CHD). Further, in patients with metabolic syndrome, hyperbilirubinemia is associated with attenuation of insulin resistance. The aim of the present study was to determine the relationship between serum bilirubin concentration and coronary endothelial function in overweight patients. METHODS: The study population consisted of 107 patients without CHD who underwent coronary flow studies. Vascular reactivity was examined by intra-coronary administration of papaverine and nitroglycerin. Coronary endothelial function was evaluated by assessing the change in coronary artery diameter to papaverine [percent change in flow-mediated dilatation (%FMD)] and nitroglycerin (%NTG). Serum total bilirubin, high-sensitivity C-reactive protein (hs-CRP), high density lipoprotein-cholesterol (HDL-C), fasting plasma glucose and immunoreactive insulin levels were also measured, and the homeostasis model assessment insulin resistance (HOMA-IR) index was calculated. Patients were divided into two groups according to body mass index (BMI): an overweight group (BMI ≥ 25; n = 36) and a normal weight group (BMI < 25; n = 71). RESULTS: In the overweight group, univariate analysis revealed that log-transformed total bilirubin was positively correlated with %FMD and HDL-C (r = 0.38, p< 0.05; r = 0.30, p < 0.05, respectively) and was inversely correlated with log-transformed hs-CRP and HOMA-IR (r = -0.45, p < 0.01; r = -0.45, p< 0.05, respectively). Multivariate analysis revealed that log-transformed hs-CRP was the only independent predictor of log-transformed total bilirubin (p< 0.05). CONCLUSIONS: These results suggest that a high bilirubin level was associated with favorable coronary endothelial function in overweight patients. Further, the anti-inflammatory effects of bilirubin may mediate this effect.

Effect of uric acid on coronary microvascular endothelial function in women: association with eGFR and ADMA.

AIM: The aim of this study was to investigate the role of uric acid (UA) in coronary endothelial function via its effects on renal function, other coronary risk factors and asymmetric dimethylarginine (ADMA) in men and women. METHODS: The study population consisted of 194 consecutive patients (119 men and 75 women) without coronary artery disease. The relationships between UA and coronary endothelial function, estimated glomerular filtration rate (eGFR), ADMA or other biochemical or anthropometric parameters were investigated. RESULTS: Monovariate analysis of female participants demonstrated that % change in coronary blood flow (CBF) induced by acetylcholine (ACh) was inversely correlated with UA, ADMA and age (r=-0.32, p<0.01; r=-0.31, p<0.05; r=-0.23, p<0.05, respectively), and positively correlated with eGFR (r=0.27, p<0.05). Stepwise regression analysis showed that UA was the only independent predictor of % change in CBF induced by ACh (F value 4.969, p<0.05). Similar analysis of male participants failed to show significant correlations of these variables except for age in monovariate analysis (r=-0.19, p<0.05). Meanwhile, UA was inversely correlated with eGFR in both men and in women (r=-0.25, p<0.01; r=-0.59, p<0.0001, respectively), and ADMA was positively correlated with UA and inversely correlated with eGFR (r=0.36, p<0.05; r=-0.42, p<0.01, respectively) in women but not in men. CONCLUSION: High concentrations of UA correlate with coronary endothelial microvascular dysfunction in women. Further, serum UA concentration is related to eGFR and ADMA only in women, which may result in impaired endothelial function in resistance coronary arteries in women but not in men.

Left atrium volume index and pathological features of left atrial appendage as a predictor of failure in postoperative sinus conversion.

BACKGROUND: Previous studies showed that some parameters, including left atrium diameter and left atrium volume index (LAVI), predicted the success of sinus conversion. However, no previous studies have investigated the association of sinus conversion with LAVI and histopathological findings. This study was designed to investigate the relationship among LAVI, pathological assessment, and failure in sinus conversion after surgery for valvular atrial fibrillation (AF). METHODS AND RESULTS: A total of 78 patients with left atrium enlargement and valvular AF who underwent maze procedure concomitantly with various cardiac surgeries were classified into one of two groups: those who successfully underwent sinus conversion (Group 1; n=40) and those who did not achieve sinus conversion (Group 2; n=38). Histopathological assessment was performed in 9 cases using tissues derived from the left atrial appendage (LAA). The degree of histopathological change was classified into 1 of 4 grades. LAVI was significantly less in Group 1 than in Group 2 (81 + or - 22 ml/m(2) vs. 122 + or - 49 ml/m(2), p<0.001). Preoperative LAVI predicted 100% failure of sinus conversion after surgery with a cut-off value of 135 ml/m(2). Histopathological analyses clearly showed that the grades for intercellular fibrosis, fatty infiltration, endocardial thickening, and nuclear enlargement/abnormalities were significantly and positively correlated with LAVI (r=0.75, p<0.05; r=0.74, p<0.05; r=0.69, p<0.05; r=0.77, p<0.05, respectively). CONCLUSIONS: LAVI associated with histopathological features of the resected LAA is a predictor of failure in sinus conversion following surgical intervention in patients with valvular AF.

Enjoying hobbies is related to desirable cardiovascular effects.

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 +/- 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% +/- 77% vs 25% +/- 37%, P < 0.05, 4% +/- 13% vs -3% +/- 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

Catheter ablation of persistent atrial fibrillation solely guided by complex fractionated atrial electrograms in a patient with persistent left superior vena cava.

Catheter ablation in patients with persistent atrial fibrillation (AF) is challenging. There are few reports of catheter ablation for persistent AF with persistent left superior vena cava (PLSVC). We report an ablation case of persistent AF with PLSVC solely guided by complex fractionated atrial electrogram (CFAE). The subject was a 65-year-old man. Electroanatomic mapping system was used to integrate computed tomography data with 3D mapping data. We identified the CFAE sites on the electroanatomic mapping. Radiofrequency ablation was applied to the CFAE sites; the posterior aspect of left superior pulmonary vein (LSPV), the anterior ridge of left atrial appendage, and the roof at the anterior to the LSPV. After those ablations, AF was finally terminated by ablation in the middle of the PLSVC. Previous investigators have reported that pulmonary vein antrum isolation (PVAI) is effective for the management of patients with either paroxysmal or persistent AF. However, some patients experience episodes of AF despite successful PVAI, which implies that important triggers and perpetuators remain in the posterior left atrium, crista terminalis, superior vena cava, coronary sinus ostium, interatrial septum, and the ligament of Marshall/PLSVC. In conclusion, CFAE ablation was useful in a patient with persistent AF with PLSVC.

High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease.

BACKGROUND: Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns to initiate an innate immune response. We previously reported upregulation of TLR2 expression level on monocytes of stable angina pectoris patients with significant coronary artery disease (CAD) relative to control patients without significant CAD. In this study we aimed to determine whether high level of Toll-like receptor 2 (TLR2) is a risk factor for atherogenesis, independent of established risk factors including smoking, diabetes mellitus (DM), hypertension (HT), and hyperlipidemia (HL). METHODS: TLR2 expression level on circulating monocyte surfaces was measured by using our developed flow cytometry assay. Patients were classified into two groups: "Arteriosclerotic disease" group (n=108) and "Control" group (n=70). Patients of the first group had arteriosclerotic disease such as CAD, aortic aneurysm, or peripheral arterial disease (PAD). The "Control" group was sex- and age-matched to the "Arteriosclerotic disease" group. RESULTS: TLR2 expression was significantly higher in the "Arteriosclerotic disease" group than in the "Control" group (p<0.001). Multivariate ordinal logistic regression analysis was performed; other known risk factors, which were represented to two nominal score points, 0 or 1, for patients with and without it, respectively, and TLR2 level, which was treated as a metric variable. DM (p=0.002), HT (p=0.001), HL (p<0.001), and TLR2 level (p<0.001) were identified as significant contributors for arteriosclerotic disease. CONCLUSIONS: High TLR2 expression level on monocytes may be an independent risk factor for atherogenesis.

Relationship between hyperglycemia and coronary vascular resistance in non-diabetic patients.

BACKGROUND: Hyperglycemia upon hospital admission in patients with acute myocardial infarction is associated with the no-reflow phenomenon after successful reperfusion, and increased mortality. However, the mechanism underlying this phenomenon remains unclear. Therefore, the aim of this study was to characterize coronary hemodynamics in a homogenous group of non-diabetic patients without coronary artery disease. METHODS AND RESULTS: A total of 104 consecutive non-diabetic patients (mean age, 62+/-14 years) without coronary artery disease underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined by intra-coronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Coronary vascular resistance (CVR) was calculated as the mean arterial pressure divided by coronary blood flow (CBF). Baseline CVR was shown as CVR at control and minimal CVR was shown as CVR with papaverine administration. Fasting plasma glucose (FPG) level had a significant, positive correlation with baseline CVR and minimal CVR (r=0.24, p<0.02 and r=0.21, p<0.05, respectively). Hemoglobin A1c (HbA1c) also had a significant, positive correlation with baseline CVR and minimal CVR (r=0.31, p<0.01 and r=0.32, p<0.01, respectively). The percent change in CBF induced by Ach was inversely correlated with HbA1c but not with FPG (r=0.22, p<0.05 and r=0.06, p=0.57, respectively). By contrast, neither FPG nor HbA1c had significant correlation with coronary flow reserve to papaverine. CONCLUSION: These data demonstrate that elevated glucose levels are associated with increases in baseline and minimal coronary vascular resistance. These changes may contribute to unfavorable coronary hemodynamics in non-diabetic patients without coronary heart disease.

Usefulness of the adenosine triphosphate with a sufficient observation period for detecting reconduction after pulmonary vein isolation.

BACKGROUND: Although reconduction after pulmonary vein (PV) isolation is considered to play a key role in the recurrence of paroxysmal atrial fibrillation (AF), there have been few reports regarding the precise time course of early reconduction. Several studies have suggested that transient PV reconduction facilitated by adenosine may predict long-term AF recurrence. This study was designed to clarify the incidence and time course of early reconduction after PVI during the procedure and to confirm whether the use of ATP after a certain observation period was useful to detect early reconduction after PVI. METHODS: In 21 patients (18 males, 56 +/- 11 years) with drug refractory AF, radiofrequency circumferential PV antrum ablation was performed in all 4 PVs. After the completion of isolation, electrograms in each PV were repeatedly recorded (1.98 +/- 0.57 times per PV) using a circular mapping catheter for an observation period of 87 +/- 29 minutes. After isolation of all 4 PVs, 30 mg of adenosine triphosphate (ATP) was administered during isoproterenol infusion. RESULTS: PV electrical isolation was initially achieved in all 81 PVs. During the observation period, 12 (15%) PVs in 10 (48%) of 21 patients exhibited spontaneous reconduction. Among the remaining 69 PVs, 8 (12%) additional PVs had reconduction with the use of ATP. All PV reconduction was successfully eliminated by 4.5 +/- 2.2 additional radiofrequency applications. CONCLUSION: A sufficient observation period and the use of ATP are useful to detect early reconduction after PV isolation.

The role of infection in the development of non-valvular atrial fibrillation: up-regulation of Toll-like receptor 2 expression levels on monocytes.

Many studies have suggested that inflammation may participate in the pathogenesis of non-valvular atrial fibrillation (AF). However, it has been unknown by exposure to what the inflammation is caused. Recently, we reported that Toll-like receptor 2 (TLR2) level on monocytes was significantly up-regulated in viral and bacterial infections, but not in non-infectious inflammatory states. Our purpose was to test the hypothesis that expression of TLR2 levels may be up-regulated in patients with non-valvular AF. A total of 48 consecutive patients with non-valvular AF who were hospitalized for catheter ablation were enrolled in this study. TLR2 levels were assayed by using flow-cytometric analysis and compared with volunteers in sinus rhythm (control group, n = 24). Additionally, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assayed, and the left atrial volume indexes (LAVI) in the non-valvular AF group were measured. The results demonstrated that TLR2 levels in the non-valvular AF group were significantly higher than in the control group (median, 4682 vs. 3866 sites/cell; P < 0.01). Moreover, non-valvular AF patients had significantly higher IL-6 levels than controls. However, there was no significant difference in CRP levels between the two groups. It was observed in 44 AF patients, in whom pulmonary vein isolation was confirmed to be successful, that the LAVI significantly diminished 1 month after ablation (median, 33.6 vs. 29.5 ml/m²; P < 0.001), but not the TLR2 and IL-6 levels. Our results implied that an infectious inflammation may participate in the pathogenesis of non-valvular AF.

Toll-like receptor 2 expression level on monocytes in patients with viral infections: monitoring infection severity.

For viral infectious diseases, reliable biomarkers capable of monitoring recovery and therapeutic effects and that simultaneously discriminate between viral and bacterial infection are necessary. In this study, by using flow-cytometric quantification system, Toll-like receptor 2 (TLR2) expression levels on monocytes of influenza patients (n=47) were compared with those of healthy volunteers (n=50). Subsequently, throughout their acute, convalescent and healed phases, TLR2, C-reactive protein (CRP), serum amyroid A (SAA), and neopterin levels were followed. Additionally, TLR2 levels in other viral infectious diseases were assayed. The results showed that TLR2 level in influenza patients was remarkably up-regulated in acute phase compared to healthy volunteers (p<0.001). Thereafter, TLR2 levels normalized in good accordance with their recovery processes. CRP and neopterin levels were relatively widely distributed from normal to abnormally high levels in acute phase in spite of similar disease severity among the patients. SAA levels did not necessarily reflect the patients' clinical course during their recovery. Clinical observations of other viral infections also indicated that TLR2 levels were compatible with infection severity. TLR2 expression level on monocytes might serve as a unique biomarker useful in viral infectious diseases.

A technique for diagnosis of accessory pathway using the H-H and A-A intervals of the first entrained cycle during ventricular overdrive pacing.

Although advancement of succeeding atrial activation by a ventricular extrastimulus (VES) on His refractoriness during supraventricular tachycardia (SVT) has been used as evidence of an accessory pathway (AP), the sensitivity of this method is suboptimal. This study was designed to compare the His-His (H-H) and atrial-atrial (A-A) intervals of the first entrained cycle during ventricular overdrive pacing (VOD) for the diagnosis of AP, in comparison to the conventional VES method. In 55 patients with SVT, a VES was elicited on His refractoriness during SVT. VOD was subsequently performed at cycle lengths 30 to 40 ms shorter than SVT cycle lengths. When the A-A interval became equal to the pacing cycle length after some beats of VOD, the cycle was considered the first entrained cycle and the H-H interval preceding the A-A interval was measured. VES advanced the next atrial activation in 16 patients (52%) with an AP, but in no patient without an AP. The H-H interval of the first entrained cycle was longer than the pacing cycle length by > or =15 ms in all patients with an AP, but was equal to the pacing cycle length in all patients without an AP. The criterion of H-H greater than A-A by > or =15 ms for the first entrained cycle provided higher diagnostic yield for AP compared with the VES method(100% vs 52%, p <0.001). In conclusion, this new criterion reliably diagnoses the presence of an AP in patients with SVT, with higher sensitivity compared with the VES method.

Comparison of effect between nitrates and calcium channel antagonist on vascular function in patients with normal or mildly diseased coronary arteries.

The comparative long-term antianginal efficacy of long-acting nitrates versus calcium channel antagonists remains unclear. The goal of the present study was to compare the coronary endothelial cell function and coronary artery vasoconstriction between patients with normal or mildly diseased coronary arteries treated with long-acting nitrates or calcium channel antagonists. Forty-two patients suspected to have angina pectoris and with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. All patients were suspected to have angina pectoris and were receiving either long-acting nitrates (n = 18; Nitrates group) or calcium channel antagonists (n = 24; Ca-antagonists group) for at least 1 year. Vascular reactivity was assessed by intracoronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Segments that showed the greatest constrictive response to Ach were used for assessment of vasoconstriction. The percent increase in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach was significantly smaller in the Nitrates group than in the Ca-antagonists group (33% +/- 74% vs 83% +/- 77%, P < 0.05; -3% +/- 16% vs 11% +/- 12%, P < 0.01, respectively). The percent diameter reduction in the region of greatest constrictive response to Ach was significantly greater in the Nitrates group than in the Ca-antagonists group (44% +/- 39% vs 15% +/- 32%, P < 0.02). Long-term treatment with long-acting nitrates may produce less favorable effects on coronary endothelial function and the constrictive response to Ach when compared with long-acting calcium channel antagonists in patients with normal or mildly diseased coronary arteries.

Adiponectin is a better predictor of endothelial function of the coronary artery than HOMA-R, body mass index, immunoreactive insulin, or triglycerides.

BACKGROUND: Previous studies have demonstrated that decreased levels of circulating adiponectin correlate with endothelial dysfunction in peripheral arteries. However, the relationship between adiponectin levels and endothelial function in coronary arteries remains unclear. The goal of the present study was to determine whether circulating adiponectin concentrations are a useful predictor of coronary endothelial function. METHODS: Thirty-six consecutive non-diabetic patients with normal or mildly diseased coronary arteries were enrolled in this study. Coronary endothelial function was evaluated by coronary vascular response to acetylcholine (Ach). The relationship between coronary vasoreactivity and adiponectin or other biochemical or anthropometric parameters was investigated. The predictive value of adiponectin level for assessment of coronary endothelial dysfunction was assessed at the best cut-off point. RESULTS: In a simple regression analysis, log-transformed adiponectin concentrations positively correlated with the percent change in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach (r=0.62, p<0.0001; r=0.63, p<0.0001, respectively). Insulin resistance index (HOMA-R), body mass index, immunoreactive insulin, and triglycerides concentrations also significantly correlated with the percent change in CBF and CAD. However, in a multiple regression analysis, log-transformed adiponectin concentration was the only independent predictor of the percent change in CBF and CAD (p<0.0001; p<0.0001, respectively). Furthermore, patients with adiponectin concentrations <6.3 mg/L demonstrated coronary endothelial dysfunction with high specificity both in terms of CBF and CAD response (85%; 88%, respectively). CONCLUSIONS: Adiponectin is a better predictor of coronary endothelial function than other factors such as HOMA-R, body mass index, immunoreactive insulin, and triglycerides.

Association between Toll-like receptors and the extent and severity of coronary artery disease in patients with stable angina.

OBJECTIVES: Toll-like receptors mediate the innate immune response triggered by pathogen-associated molecular patterns, and atherosclerosis can be considered a state of chronic inflammation whereby immune system cells accumulate within the intima of the arterial wall. The goal of this study was to determine the relation of Toll-like receptors to the extent and severity of coronary artery disease. METHODS: Angiographic vessel score and Gensini score were used to evaluate the extent and severity of coronary atherosclerosis. Sixty-two consecutive patients with stable angina were grouped as follows: those with insignificant (<50%) coronary stenosis (group 1), and those with 1 (group 2), 2 (group 3), or 3-vessel disease (group 4). The expression of Toll-like receptor 1, 2, and 4 on circulating CD14+ monocytes was analyzed by flow-cytometry in all patients. RESULTS: Toll-like receptor 2 had a positive correlation with the vessel score and Gensini score (r=0.46, P<0.001; r=0.32, P<0.02, respectively). Toll-like receptor 4 also positively correlated with the vessel score and Gensini score (r=0.47, P<0.001; r=0.29, P<0.05, respectively). No significant correlation existed between the expression of Toll-like receptor 1 and the vessel score or Gensini score. Further, there was no significant correlation between high-sensitivity C-reactive protein and the vessel score or Gensini score. CONCLUSION: These data suggest that Toll-like receptor 2 and 4 expression correlates with the extent and severity of coronary artery disease.