Clinical impact of Academic Research Consortium for High Bleeding-Risk scores on clinical outcomes in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

High bleeding risk (HBR), as defined by the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria, has been recently reported to be associated with an increased risk of major bleeding events and cardiovascular events. We investigated the association between the ARC-HBR score and clinical outcomes in patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). We assessed 328 consecutive patients with stable CAD who underwent PCI between January 2017 and December 2020. We scored the ARC-HBR criteria by assigning 1 point to each major criterion and 0.5 points to each minor criterion. Patients were stratified into low (ARC-HBR score < 1), intermediate (1 ≤ ARC-HBR score < 2), and high (ARC-HBR score ≥ 2) bleeding-risk groups. The primary outcome measure was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. We compared the discriminative abilities of the ARC-HBR score with the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) and ARC-HBR score with Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic risk score. The mean patient age was 70.1 ± 10.2 years (males, 76.8%). During the median follow-up period of 983 (618-1338) days, 44 patients developed MACE. Kaplan-Meier curves showed that a stepwise significant increase in the cumulative incidence of MACE as the ARC-HBR score increased (log-rank p < 0.001). In the time-dependent receiver-operating characteristic curve analysis for predicting MACE within 2 years, the area under the curve (AUC) of the ARC-HBR score was significantly higher than that of the TRS2°P (AUC: 0.825 vs. 0.725, p value for the difference = 0.023) and similar to that of CREDO-Kyoto thrombotic risk score (AUC: 0.825 vs. 0.813, p value for the difference = 0.627). Conclusions: The ARC-HBR score adequately stratified future risk of MACE in patients with stable CAD who underwent PCI. The ARC-HBR score showed a higher discriminative ability for predicting mid-term MACE than the TRS2°P.

Comparison of Discriminative Ability of Bleeding Risk Criteria and Scores for Predicting Short- and Mid-Term Major Bleeding Events in Patients Undergoing Percutaneous Coronary Intervention.

Background: This study aimed to compare the discriminative ability of the Japanese Version of High Bleeding Risk (J-HBR), Academic Research Consortium for High Bleeding Risk (ARC-HBR), and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) scores for predicting major bleeding events. Methods and Results: Between January 2017 and December 2020, 646 consecutive patients who underwent successful percutaneous coronary intervention (PCI) were enrolled. We scored the ARC-HBR and J-HBR criteria by assigning 1 point to each major criterion and 0.5 point to each minor criterion. The primary outcome was major bleeding events, defined as Bleeding Academic Research Consortium type 3 or 5 bleeding events. According to the J-HBR, ARC-HBR, and PRECISE-DAPT scores, 428 (66.3%), 319 (49.4%), and 282 (43.7%) patients respectively had a high bleeding risk. During the follow-up period (median, 974 days), 44 patients experienced major bleeding events. The area under the curve (AUC) using the time-dependent receiver operating characteristic curve for major bleeding events was 0.84, 0.82, and 0.83 within 30 days and 0.86, 0.83, and 0.80 within 2 years for the J-HBR, ARC-HBR, and PRECISE-DAPT scores, respectively. The AUC values did not differ significantly among the 3 bleeding risk scores. Conclusions: The J-HBR score had a discriminative ability similar to the ARC-HBR and PRECISE-DAPT scores for predicting short- and mid-term major bleeding events.

Cardio-Ankle Vascular Index and Left Atrial Reverse Remodeling After Ablation for Atrial Fibrillation.

Arterial stiffness has been reported to cause left atrial (LA) remodeling due to increased left ventricular filling pressure, resulting in atrial fibrillation (AF). This study aimed to evaluate the association between LA reverse remodeling (LARR) after AF ablation and cardio-ankle vascular index (CAVI), an indicator of arterial stiffness.This study included 333 patients with AF (171 with paroxysmal AF and 162 with nonparoxysmal AF) and LA enlargement (LA volume index ≥ 34 mL/m2) who underwent AF ablation between December 2008 and July 2021. CAVI was evaluated preoperatively during AF (n = 155, 46.5%) or sinus rhythm (n = 178, 53.5%). Participants were divided into groups with LARR (n = 133, 39.9%) and without LARR (n = 200, 60.1%) according to whether the degree of decrease in LA volume index on transthoracic echocardiography 6 months after ablation was ≥ 15% or < 15%, respectively.Sinus rhythm was maintained in 168 (50.5%) patients within 3-6 months after the index procedure. Univariate analysis revealed that preoperative CAVI (7.80 ± 1.22 versus 8.57 ± 1.09, P < 0.001) was significantly lower, and the maintenance of sinus rhythm (61.6% versus 43.0%, P = 0.0011) was higher in the group with LARR. Multivariate logistic regression analysis revealed that preoperative CAVI was independently associated with LARR (odds ratio, 0.60, 95% confidence interval, 0.46-0.78, P < 0.001).In patients with AF and LA enlargement, CAVI is independently associated with LA reverse remodeling after catheter ablation.

Association of preoperative clinical frailty and clinical outcomes in elderly patients with stable coronary artery disease after percutaneous coronary intervention.

There are few reports on the long-term clinical outcome after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) complicated with frailty. This novel study investigated the association between pre-PCI frailty and long-term clinical outcomes in elderly patients aged 65 years or older with stable CAD who underwent elective PCI. We assessed 239 consecutive patients aged 65 years or older with stable CAD who underwent successful elective PCI at Kagoshima City Hospital between January 1st, 2017 and December 31st, 2020. Frailty was retrospectively assessed using the Canadian Study and Aging Clinical Frailty Scale (CFS). Based on the pre-PCI CFS, patients were divided into two groups: the non-frail (CFS < 5) and the frail (CFS ≥ 5) group. We investigated the association between pre-PCI CFS and major adverse cardiovascular events (MACEs) defined as the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and heart failure requiring hospitalization. Additionally, we assessed the association between pre-PCI CFS and major bleeding events defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The mean age was 74.8 ± 7.0 years, and 73.6% were men. According to the pre-PCI frailty assessment, 38 (15.9%) and 201 (84.1%) were classified as frail and non-frail groups, respectively. During a median follow-up of 962 (607-1284) days, 46 patients developed MACEs and 10 patients developed major bleeding events. Kaplan-Meier curves showed a significantly higher incidence of MACE in the frail group compared to those in the non-frail group (Log-rank p < 0.001). Even in multivariate analysis, pre-PCI frailty (CFS ≥ 5) was independently associated with MACE (HR 4.27, 95% CI 1.86-9.80, p-value: < 0.001). Additionally, the cumulative incidence of major bleeding events was significantly higher in the frail group than in the non-frail group (Log-rank p = 0.001). Pre-PCI frailty was an independent risk factor for MACE and bleeding events in elderly patients with stable CAD who underwent elective PCI.

Adventitial Cystic Disease in the Popliteal Artery Diagnosed by Intravascular Ultrasound Imaging.

The prevalence of peripheral artery disease (PAD) has been increasing in parallel with the increasing prevalence of the atherosclerotic disease. Therefore, we have to be familiar with the diagnostic approach used for ischemic symptoms in the lower limbs. Adventitial cystic disease (ACD) is rare but not negligible as one of the differential diagnoses of intermittent claudication (IC). Although duplex ultrasound and magnetic resonance imaging (MRI) are helpful tools for the diagnosis of ACD, further imaging modality is needed to avoid misdiagnosis. A 64-year-old man with a mitral valve prosthesis presented to our hospital with a one-month history of IC in the right calf after walking for approximately 50 meters. On physical examination, the pulse in the right popliteal artery was not palpable, nor were the dorsal pedis artery and posterior tibial artery, although there were no other symptoms of ischemia. His right ankle-brachial index (ABI) was 1.12 at rest but decreased to 0.50 after exercise. Three-dimensional computed tomography (CT) angiography revealed a severe stenotic lesion approximately 70 mm long in the right popliteal artery. Therefore, we diagnosed PAD in the right lower limb and planned endovascular therapy. The stenotic lesion was markedly reduced on catheter angiography when compared with CT angiography. However, intravascular ultrasound (IVUS) detected little atherosclerosis and cystic lesions within the wall in the right popliteal artery that did not involve the arterial lumen. Especially, IVUS clearly demonstrated that the crescent-shaped cyst compressed the arterial lumen eccentrically and other cysts surrounded the lumen circumferentially like petals. Because IVUS revealed these cysts to be extravascular structures, the patient was subsequently thought to have ACD of the right popliteal artery. Fortunately, his cysts reduced in size spontaneously and his symptoms disappeared. We have monitored the patient's symptoms, ABI, and findings on duplex ultrasound for seven years, during which there has been no recurrence. In this case, we diagnosed ACD in the popliteal artery by IVUS rather than duplex ultrasound and MRI.

Association between the number of Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria and clinical outcomes in patients with acute coronary syndrome.

BACKGROUND: Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria have been used to identify high-risk patients undergoing percutaneous coronary intervention (PCI) in current clinical practice. This study aimed to evaluate the association between the number of ARC-HBR criteria and clinical outcomes in patients with acute coronary syndrome (ACS) after an emergent PCI. METHODS: We assessed 338 consecutive patients with ACS who underwent successful emergent PCI between January 2017 and December 2020. The ARC-HBR score was calculated by assigning 1 point to each major criterion and 0.5 points to each minor criterion. The patients were classified into low (ARC-HBR score<1), intermediate (1≤ARC-HBR score<2), and high (ARC-HBR score≥2) bleeding risk groups. We investigated the association between the ARC-HBR score and major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke. We also compared the diagnostic ability of the ARC-HBR score and Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) risk score. RESULTS: The mean age of the patients was 67.6±12.4years, and 78.4% were men. During the median follow-up of 864 (557-1309) days, 70 patients developed MACEs. Kaplan-Meier curves showed that the cumulative incidence of MACE was significantly higher as the ARC-HBR score increased in a stepwise manner (log-rank p<0.001). There were no significant differences in the area under the receiver operating characteristic curve (AUC) for predicting MACE within two years after an emergent PCI between the ARC-HBR and CADILLAC risk scores (AUC: 0.763 vs. 0.777). CONCLUSIONS: ARC-HBR score was independently associated with an increased risk of MACE in patients with ACS after an emergent PCI. Moreover, it had a similar diagnostic ability for predicting MACE within two years compared to the CADILLAC risk score.

A randomized comparison of two direct oral anticoagulants for patients undergoing cardiac ablation with a contemporary warfarin control arm.

BACKGROUND: The safety and efficacy of periprocedural use of direct oral anticoagulants (DOACs) for atrial fibrillation (AF) remain unclear. We compared the incidence of asymptomatic cerebral micro-thromboembolism and hemopericardium following AF ablation among patients receiving edoxaban, rivaroxaban, and warfarin and between normal- and low-dose use of edoxaban and rivaroxaban. METHODS: This prospective randomized study included 170 consecutive AF patients. Patients taking DOACs upon admission to our hospital were randomly assigned to an edoxaban group or to a rivaroxaban group. Warfarin was continued in patients receiving warfarin at admission. All patients underwent AF ablation, and cerebral MRI was performed to evaluate asymptomatic cerebral micro-thromboembolism the day after the procedure. RESULTS: Sixty-one patients were assigned to edoxaban and 63 to rivaroxaban. Warfarin was continued in 46 patients. Although asymptomatic cerebral micro-thromboembolism was detected in 25 patients (16.3%), there were no significant differences among the groups. Hemopericardium occurred in 2 patients (one each in the rivaroxaban and warfarin groups). The incidence of asymptomatic cerebral micro-thromboembolism was higher in the low-dose group (9 patients, 25.7%) than in the normal-dose group (8 patients, 10.0%) for patients prescribed either edoxaban or rivaroxaban (p < 0.05). The proportion of males (88.0%, 69.5%, p < 0.05), history of prior AF ablation (64.0%, 42.2%, p < 0.05), and hypertension (68.0%, 46.1%, p < 0.05) were significantly higher in patients with cerebral thromboembolism. CONCLUSIONS: The incidence of asymptomatic cerebral micro-thromboembolism and hemopericardium in AF ablation was similar among patients using edoxaban, rivaroxaban, and warfarin. However, low doses of DOACs may increase the risk of asymptomatic stroke.

Dynamics of Soluble Thrombomodulin and Circulating miRNAs in Patients with Atrial Fibrillation Undergoing Radiofrequency Catheter Ablation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world and has a high risk of thromboembolism. The most effective approach, catheter ablation, requires evaluation by electrocardiography. The aim of our study was to investigate novel clinical markers that predict restoration of sinus rhythm (SR) after catheter ablation. Seventy-eight consecutive patients with AF underwent catheter ablation and were separated into 2 groups: restored SR and recurrent AF. The levels of 4 blood proteins (serum or plasma) and 3 mature microRNAs (miRNAs) and their primary miRNAs (pri-miRNAs) in serum were measured before and after ablation, and the associations between each parameter were analyzed statistically. Soluble thrombomodulin (s-TM) and plasminogen activator inhibitor-1 (PAI-1) levels increased above baseline after ablation in both the restored SR (s-TM 11.55 [2.92] vs 13.75 [3.38], P < .001; PAI-1 25.74 [15.25] vs 37.79 [19.56], P < .001) and recurrent AF (s-TM 10.28 [2.78] vs 11.67 [3.37], P < .001; PAI-1 26.16 [15.70] vs 40.74 [22.55], P < .001) groups. Levels of C-reactive protein and asymmetric dimethylarginine were not significantly changed. Pri-miR-126 levels significantly decreased after ablation in the recurrent AF group, but the other miRNAs and pri-miRNAs did not. The measurement of s-TM and pri-miR-126 in blood was a useful tool to reflect the condition of AF patients with catheter ablation.

Evaluation of safety and efficacy of periprocedural use of rivaroxaban and apixaban in catheter ablation for atrial fibrillation.

BACKGROUND: We previously reported that dabigatran increased the risk of microthromboembolism and hemopericardium compared with warfarin. The safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in the periprocedural use of atrial fibrillation (AF) ablation is controversial. This study aimed to compare the incidence of asymptomatic cerebral microthromboembolism and hemopericardium in AF ablation among periprocedural use of rivaroxaban, apixaban, and warfarin. METHODS AND RESULTS: This study was a prospective, randomized registry. Patients taking NOACs upon visiting our hospital were randomly assigned into 2 groups; rivaroxaban and apixaban. Warfarin was continued in patients taking warfarin. Asymptomatic cerebral microthromboembolism was evaluated by magnetic resonance imaging on the day after the ablation procedure. In 176 consecutive patients (101 paroxysmal, and 75 persistent AF), rivaroxaban was used in 55, apixaban in 51, and warfarin in 70. There were no symptomatic cerebral infarctions in this study. Asymptomatic cerebral microthromboembolism was detected in 32 (18.4%) patients; nine (16.4%) with rivaroxaban, 10 (20%, p=0.80; vs. rivaroxaban) with apixaban, and 13 (18.8%, p=0.81; vs. rivaroxaban) with warfarin. Hemopericardium occurred in 5 (2.8%) patients; 2 with rivaroxaban, 1 with apixaban (p=1.0; vs. rivaroxaban), and 2 with warfarin (p=1.0; vs. rivaroxaban). In multivariate analysis, concomitant coronary angiography (p<0.05, odds ratio 5.73) was a predictor of cerebral thromboembolism. CONCLUSIONS: The incidence of asymptomatic cerebral microthromboembolism and hemopericardium in AF ablation is similar among the periprocedural use of rivaroxaban, apixaban, and warfarin.

The optimal setting of complex fractionated atrial electrogram software in substrate ablation for atrial fibrillation.

BACKGROUND: Complex fractionated atrial electrogram (CFAE)-targeted catheter ablation (CFAE ablation) requires a high rate of atrial fibrillation (AF) termination to provide good outcomes. We determined the optimal settings of CFAE software. METHODS: In our 430 consecutive patients, AF was terminated in 97 (234/242) and 79% (149/188) of patients with paroxysmal and persistent AF, respectively, by CFAE ablation combined with (31%) or without (69%) pulmonary vein isolation, occasionally with nifekalant infusion. We analyzed 109 consecutive patients who underwent CFAE ablation to determine the optimal settings for comparing subjective versus objective decisions by the CFAE software on CARTO3. We compared three settings: the default setting (0.05-0.15 mV, 50-120 ms) and two modified settings (#1: 0.05-0.30 mV, 40-70 ms, #2: 0.05-0.13 mV, 10-20 ms). We retrospectively analyzed 11,425 points during left atrial mapping before ablation and 10,306 points that were subjectively detected and ablated as CFAE points. An interval confidence level ≥6 denoted a site with CFAE. RESULTS: With the default setting, the accuracy, sensitivity, specificity, positive productive value, and negative productive values were 67, 42, 77, 48, and 73%, respectively. With modified setting #1, the values were 78, 55, 87, 74, and 77%, respectively, versus 64, 82, 60, 53, and 91%, respectively, for modified setting #2. CONCLUSION: These data suggest that setting #1 was generally superior to the default setting, whereas setting #2 was optimal for excluding areas not requiring ablation. The optimal CFAE software setting was a voltage of 0.05-0.30 mV and an interval parameter of 40-70 ms.

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.

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.

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.