Reproducibility of cardiopulmonary exercise testing between one after and 1-3 weeks after elective percutaneous coronary intervention.

Prompt prescription and early initiation of exercise training are essential for patients undergoing elective percutaneous coronary intervention (PCI). We hypothesized that cardiopulmonary exercise testing (CPET) parameters determined the day after elective PCI during hospitalization would not differ from those obtained 1-3 weeks post-PCI in patients with stable coronary heart disease (CHD). CPET was performed the day after and 1-3 weeks (13±4.6; 7-21 days) after PCI. CPET was performed with a bicycle ergometer up to the ventilatory aerobic threshold (VAT) on the day after PCI. Symptom-limited CPET was conducted 1-3 weeks after PCI. No complications arose from the tests. There were no significant differences in %VAT (next day: 88.6±16.7 vs. 1-3 weeks later: 91.4%±18.7%), the workload at the VAT (51.8±11.0 W vs. 52.9± 11.6 W), heart rate (HR) at the VAT (95.3±105 beats/min vs. 94.1±11.3 beats/min), or metabolic equivalent (METs) at the VAT (3.69±0.69 vs. 3.84±0.78) between the two sessions. The slope of linear regression for two repeated measurements was close to 1 (%VAT, 1.02; workload at the VAT, 0.95; METs at the VAT, 1.03), except for HR (0.70). Bland-Altman plots revealed the reproducibility of all four CPET measurements between the two sessions. In conclusion, CPET up to the VAT can be performed safely 1-day post-PCI in patients with stable CHD. CPET parameters do not significantly differ between testing performed the day after and 1-3 weeks after PCI. Next-day CPET during hospitalization after PCI may enable prompt exercise prescription without the need for another CPET 1-3 weeks later.

Small solitary atrial fractionated electrogram zone as a novel ablation target for persistent atrial fibrillation.

INTRODUCTION: Various adjunctive approaches to pulmonary vein isolation (PVI) have been attempted for persistent atrial fibrillation (perAF) and longstanding persistent AF (ls-perAF). We aimed to identify the novel zones responsible for perpetuation of AF. METHODS: To identify novel zones acting as a source of perAF and ls-perAF after PVI/re-PVI, we performed fractionation mapping in 258 consecutive patients with perAF (n = 207) and ls-perAF (n = 51) in whom PVI/re-PVI failed to restore sinus rhythm. RESULTS: In 15 patients with perAF (5.8%: 15/258), fractionation mapping identified a small solitary zone (<1 cm2 ) with high-frequency and irregular waves, showing fractionated electrograms (EGM). We defined this zone as the small solitary atrial fractionated EGM (SAFE) zone. The small SAFE zone was surrounded characteristically by a homogeneous area showing relatively organized activation with nonrapid and nonfractionated waves. Only one small SAFE zone was detected in each patient. This characteristic electrical phenomenon was observed stably during the procedure until ablation. AF duration, (defined as the duration between initial detection of AF and the current ablation) was longer in patients with the small SAFE zone than in those without (median, [25 and 75 percentiles]; 5.0 [3.5, 7.0] vs. 1.1 [1.0, 4.0] years, p = .0008). Longer AF cycle length was observed in patients with the small SAFE zone than in those without. The ablation of the small SAFE zone terminated AF in all 15 patients without any need for other ablations. AF/atrial tachycardia-free rate at follow-up was 93% (14/15) at 6 months, 87% (13/15) at 1 year, and 60% (9/15) at 2 years. CONCLUSIONS: Using fractionation mapping, this study identified a small SAFE zone surrounded characteristically by a homogeneous, relatively organized, low-excitability EGM lesion. The ablation of the small SAFE zone terminated AF in all patients, demonstrating it as a substrate for perpetuated AF. Our findings provide novel ablation targets in perAF patients with prolonged AF duration. Further studies to confirm the present results are warranted.

Optimal prevention method of phrenic nerve injury in superior vena cava isolation: efficacy of high-power, short-duration radiofrequency energy application on the risk points.

BACKGROUND OR PURPOSE: Superior vena cava isolation (SVCI) is widely performed adjunctively to atrial fibrillation (AF) ablation. Right phrenic nerve injury (PNI) is a complication of this procedure. The purpose of the study is to determine the optimal PNI prevention method in SVCI. METHODS: A total of 1656 patients who underwent SVCI between 2009 and 2022 were retrospectively examined. PNI was diagnosed based on the diaphragm position and movement in the upright position on chest radiographs before and after SVCI. RESULTS: With the introduction of various PN monitoring systems over the years, the incidence of SVCI-associated PNI has decreased. However, complete PNI avoidance has not been achieved. PNI incidence according to fluoroscopy-guided PN monitoring, high-output pace-guided, compound motor action potential-guided, and 3-dimensional electro-anatomical mapping (EAM) systems was 8.1% (38/467), 2.7% (13/476), 2.4% (4/130), and 2.8% (11/389), respectively. However, a high-power, short-duration (50 W/7 s) radiofrequency (RF) energy application only on PNI risk points tagged by a 3-dimensional EAM system completely avoids PNI (0%; 0 /160 since April 2021). PNI showed no symptoms and recovered within an average of 188 days post-SVCI, except for a few patients who required > 1 year. CONCLUSIONS: Although PNI incidence decreased annually with the introduction of various monitoring systems, these monitoring systems did not prevent PNI completely. Most notably, the delivery of a high-power, short-duration RF energy only on risk points tagged by EAM prevented PNI completely. PNI recovered in all patients. The application of higher-power, shorter-duration RF energy on risk points tagged by EAM appears to be an optimal PNI prevention maneuver.

Rates of atrial flutter occurrence and cavotricuspid isthmus reconduction after prophylactic isthmus ablation performed during atrial fibrillation ablation: a clinical study, review, and comparison with previous findings.

PURPOSE: Based on the high rate of coexisting atrial fibrillation (AF) and atrial flutter (AFL), prophylactic cavotricuspid isthmus ablation (CTIA) adjunctive to AF ablation has recently been attempted in patients with AF and without AFL. The present study aimed to determine the rates of AFL occurrence and CTI reconduction after performing CTI ablation adjunctive to AF ablation. METHODS: We analyzed the data of 3833 consecutive patients with AF, who underwent prophylactic CTIA with AF ablation between 2009 and 2020. RESULTS: In all patients, CTIA and AF ablations were successful. Clinical AFL occurred in seven patients (0.18%, 7/3,833), and the observed rate was lower than those reported for cases of AF ablation without CTIA and for those of CTIA for pure AFL. A second ablation was needed in 745 patients at a median of 253 days (25 and 75 percentiles, 116 and 775 days) after the first ablation. In 12.1% (90/745) of the patients, CTI reconduction was observed. The reconduction rate was lower than that previously reported for CTIA for pure AFL. CONCLUSIONS: The present retrospective study found acceptably low rates of clinical AFL occurrence and CTI reconduction following prophylactic CTIA performed with AF ablation, which was supported by the findings obtained after performing a comparison of the rates with those of other ablations (AF ablation only and CTIA for pure AFL). Considering the high correlation between AF and AFL, the present study provided information regarding the efficacy of adjunctive CTIA.

Efficacy of an Adjunctive Electrophysiological Test-Guided Left Atrial Posterior Wall Isolation in Persistent Atrial Fibrillation Without a Left Atrial Low-Voltage Area.

BACKGROUND: Electrical remodeling precedes structural remodeling. In adjunctive left atrial (LA) low-voltage area (LVA) ablation to pulmonary vein isolation of atrial fibrillation (AF), LA areas without LVA have not been targeted for ablation. We studied the effect of adjunctive LA posterior wall isolation (PWI) on persistent AF without LA-LVA according to electrophysiological testing (EP test). METHODS: We examined consecutive patients with persistent AF with (n=33) and without (n=111) LA-LVA. Patients without LA-LVA were randomly assigned to EP test-guided (n=57) and control (n=54) groups. In the EP test-guided group, an adjunctive PWI was performed in those with positive results (PWI subgroup; n=24), but not in those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, effective refractory period>20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia (AT) during measurements. LVA ablation was performed in the patients with LA-LVA. RESULTS: During the follow-up period (62±33 weeks), the EP test-guided group had significantly lower recurrence rates (19%,11/57 versus 41%, 22/54, P=0.012) and higher Kaplan-Meier AF/AT-free survival curve rates than the control group (P=0.01). No significant differences in the recurrence and AF/AT-free survival curve rates between the PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analyses identified EP test-guided ablation as a factor reducing the recurrence rate. The recurrence rates in the LA-LVA ablation group and EP test-guided group were similar. CONCLUSIONS: This pilot study proposed that an EP test-guided adjunctive PWI of persistent AF without LA-LVA potentially reduced AF/AT recurrences. The results suggest that there is an AF substrate in the LA with altered electrophysiological function even when there is no LA-LVA. Graphic Abstract: A graphic abstract is available for this article.

Correlation of the peak oxygen consumption and ventilatory aerobic threshold by cardiopulmonary exercise testing with atrial fibrillation recurrences after ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The cardiopulmonary function is hypothesized to be associated with atrial fibrillation/atrial tachyarrhythmia (AF/AT) recurrence after AF ablation. PURPOSE: To clarify the relationship between the cardiopulmonary function after successful ablation and AF/AT recurrence. METHODS: We examined 31 patients with paroxysmal AF who underwent AF ablation. Cardiopulmonary exercise testing (CPET) was performed at 1month after the ablation. A continuously increasing loading method on a bicycle ergometer was employed for the CPET. RESULTS: No adverse events, including AF/AT recurrence, occurred during the CPET. Among 31 patients, AT/AF recurrence was observed in seven (23%). The ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO2) were significantly higher in patients without AF/AT recurrence than in those with AT/AF recurrences (peak VO2 23.6 ± 5.7 vs 17.2 ± 4.1 mL/kg/min; VAT, 16.7 ± 2.8 vs 13.8 ± 2.7 mL/min/kg). The areas under the receiver operating characteristic curve for the peak VO2 and VAT were 0.786 (P < .01) and 0.789(P < .01), respectively. Both indices had a sensitivity of 70%-80% and specificity of 70%-80% for predicting AT/AF recurrence. Similar results were obtained for the percent values of the predicted peak VO2 and VAT. CONCLUSIONS: The present pilot study found that CPET can be performed safely at approximately 1 month after AF ablation. The peak VO2 and VAT were significantly associated with AT/AF recurrence. The peak VO2 and VAT were thought to provide helpful information regarding AT/AF recurrence.

Activated clotting time on the day of atrial fibrillation ablation for minimally interrupted and uninterrupted direct oral anticoagulation therapy: Sequential changes, differences among direct oral anticoagulants, and ablation safety outcomes.

BACKGROUND: Activated clotting time (ACT)-guided heparinization is used during atrial fibrillation (AF) ablation. Differences in sensitivity to ACT assays have been identified among different direct oral anticoagulants (DOACs). OBJECTIVE: We aimed to examine ACT just before ablation (pre-ACT) for different ablation start times (9:00, 11:00, 13:00, or 15:00) and ablation safety outcomes in minimally interrupted (min-Int) and uninterrupted (Unint) DOAC regimens and examine differences in pre-ACT values among four DOACs. METHODS: Consecutive patients were randomized into the min-Int (n = 307) or Unint (n = 277) groups. DOACs examined were apixaban, dabigatran, edoxaban, and rivaroxaban. RESULTS: No sequential changes in pre-ACT values were observed for each DOAC used and for all four DOACs combined in the min-Int and Unint groups. There was no meaningful difference in pre-ACT at each ablation start time between the groups. Clinically significant differences in overall pre-ACT were not obtained between the groups (138 ± 24 vs 142 ± 23 seconds). The pre-ACT (baseline) value for dabigatran was on average 29 seconds higher than that for the other three DOACs. The min-Int and Unint groups showed similar thromboembolic (0% vs 0%) and bleeding event rates (major, 1% vs 0%; all, 3.5% vs 2.5%). CONCLUSION: The pre-ACT did not show a sequential change in the min-Int and Unint groups. No notable differences in the time-dependent change in pre-ACT between the groups were observed. Variations in baseline ACT suggest the need for moderate adjustment of ACT for adequate modification of heparin dose for the other three DOACs. Both regimens provided similar acceptable AF ablation safety outcomes.

Effects of Oral Anticoagulants on Patients With Atrial Fibrillation Aged 90 Years and Older: Comparison Among Direct Oral Anticoagulant, Warfarin Anticoagulant, and Nonanticoagulation.

This study aimed to investigate the effects of anticoagulants on ultra-aged patients with nonvalvular atrial fibrillation (AF). We retrospectively studied 320 consecutive patients with AF (median age, 91 years; range 90-100.1 years). Patients were categorized as follows: patients taking direct oral anticoagulant (DOAC group, n = 93), those taking warfarin (warfarin group, n = 147), and those not taking oral anticoagulants (non-OAC group, n = 80). During the follow-up periods (median 3.00 years; first and fourth quantiles, 1.13 and 4.56 years, respectively), in thromboembolic events, the DOAC, warfarin, and non-OAC groups showed the lowest (0%, 0/93; 0%/year), intermediate (4.7%, 7/149; 1.43%/year), and highest (5%, 4/80; 2.65%/year) incidence rates, respectively. In major bleeding events, the DOAC, warfarin, and non-OAC groups showed the highest (9.67%, 9/96; 5.00%/year), intermediate (8.1%, 12/149; 2.46%/year), and lowest (0%, 0/80; 0%/year) incidence rates, respectively. These differences in the relationships of the 3 groups were statistically significant. Confounding factors did not affect these results. Bruises associated with impairment of motor function with aging caused major bleeding in approximately 60% of major bleeding cases. The Cox proportional hazards model revealed that warfarin decreased mortality, whereas antiplatelet drugs increased mortality. In conclusion, DOACs had considerably high incidence of major bleeding events, whereas absence of OAC treatment was associated with substantially high thromboembolic events. Warfarin showed acceptable incidence ratios of both events. At present, warfarin is thus believed to be adequate for ultra-aged (≥90 years) patients with nonvalvular AF. Avoidance of bruises was important to prevent major bleeding events. Antiplatelet drugs were suggested not to be adequate for these patients.

Adjunctive left anterior line ablation induced left atrial dysfunction and dyssynchrony in atrial fibrillation ablation.

We evaluated the effects of adjunctive left anterior line (LAL) ablation on LA dyssynchrony and function using real-time three-dimensional echocardiography (3DE) in connection with thromboembolic complications and tachyarrhythmia recurrence in patients with persistent atrial fibrillation (AF). We randomly and prospectively assigned consecutive persistent AF patients to the LAL (n = 52, 65 ± 7 years) and control groups (n = 50, 64 ± 10 years). In the LAL group, extensive encircling pulmonary vein isolation (EEPVI), roof line ablation, and LAL ablation regardless of the extent of the low-voltage area (LVA) were performed. The control group underwent EEPVI and roof line ablation. After ablation, 3DE demonstrated LA dyssynchrony in 23 (46%) and 4 patients (8%, P < 0.001) of the LAL and control groups, respectively. Baseline LA LVAs were relatively small in most patients and there were no significant differences in extent of LVA between control and LAL groups or between patients with and without dyssynchrony. During the follow-up periods (771 ± 121 days), patients with LA dyssynchrony in the LAL group did not show significant differences in symptomatic thromboembolic events (0%) and atrial tachyarrhythmia recurrence (39%) from patients without LA dyssynchrony in the LAL (0% and 30%) and control groups (0% and 32%, respectively). LA ejection fraction and active emptying fraction were lower by 9% on average in the LAL group than in the control group (P < 0.0001). Similarly, in the LAL group, LA ejection fraction, active emptying fraction, and expansion index were significantly lower by approximately 7%, 8%, and 15%, respectively, in LA with dyssynchrony than those in LA without dyssynchrony. In conclusion, LA dyssynchrony and LA hypofunction were induced by LAL ablation in patients with persistent AF and relatively mild LVA. LAL ablation with or without LA dyssynchrony is thought not to affect thromboembolic complications or atrial tachyarrhythmia recurrence.

Differences in activated clotting time and initial heparin dosage during atrial fibrillation ablation for patients with edoxaban compared with warfarin.

BACKGROUND: Different target activated clotting times (ACTs) during atrial fibrillation (AF) ablation have been proposed. Moreover, relationships between initial bolus dose of heparin at the start of AF ablation in patients receiving edoxaban anticoagulation therapy and ACT are unclear. METHODS: Patients who received anticoagulation with uninterrupted warfarin (control; n = 120) or interrupted edoxaban (n = 120) on the morning of day of ablation were studied. An initial dose of 100 U/kg heparin was administered as a reliable control for warfarin. Initial heparin doses of 120, 130, 140, or 150 U/kg were randomly administered to the edoxaban group. RESULTS: Edoxaban group showed shorter baseline ACT before the procedure (130 ± 16 seconds) than the warfarin group (152 ± 26 seconds, P < 0.0001). In the warfarin group, 100 U/kg heparin showed 361 ± 48 seconds 15-minute ACT. In the edoxaban group, an increase in initial dose induced prolongation of 15-minute ACT (i.e., 15-minute ACTs of 293 ± 56, 306 ± 39, 311 ± 45, and 319 ± 45 seconds for 120, 130, 140, and 150 U/kg initial doses, respectively). The total heparin required during the procedure was higher in the edoxaban group than in the warfarin group (109 ± 37 vs. 77 ± 21 U/kg/h, P < 0.0001). The 120-150 U/kg dose of heparin in edoxaban group did not cause thromboembolic or major bleeding complications. CONCLUSION: Edoxaban interrupted on the day of ablation showed a shorter baseline ACT than uninterrupted warfarin. Edoxaban required a higher initial heparin dose to achieve a similar 15-minute ACT to warfarin. These results are useful for determining the initial heparin dose required to achieve variable target ACTs.

Adjunctive interpulmonary isthmus ablation has no added effects on atrial fibrillation recurrence.

OBJECTIVE: Data on the efficacy of adjunctive interpulmonary isthmus ablation following completion of extensive encircling pulmonary vein isolation (EEPVI) on atrial fibrillation (AF) recurrence have still been insufficient. We aimed to compare the AF recurrence between EEPVI with and without adjunctive interpulmonary isthmus ablation. METHODS: We enrolled 200 consecutive patients with paroxysmal AF (first session) who underwent EEPVI with double-Lasso technique. Patients were prospectively randomised into two groups: EEPVI with (group 1) and without (group 2) adjunctive interpulmonary isthmus ablation. RESULTS: No differences were found in patients' clinical and echocardiographic backgrounds, including arrhythmia status, between the two groups. No differences were also observed in complications (two groin haematoma in both groups). All patients in both groups reached the EEPVI endpoint. The AF recurrence rate between groups 1 (32/100, 32%) and 2 (33/100, 33%; p=1.0) was quite similar during the follow-up period (45±5 months; 36-54 months). The two groups showed identical Kaplan-Meier AF-free curves (p=0.460; NS). Similar pulmonary vein (PV) reconnection incidence was observed in both groups during the second session. Durable isolation between the superior and inferior PVs was confirmed in 88% (21/27) of patients in group 1, indicating that interpulmonary isthmus ablation maintained a non-conducting state in a considerable number of patients. Nevertheless, AF recurrence was identical between the two groups. CONCLUSION: The results of our study showed similar AF recurrence rates between the two groups, indicating that adjunctive interpulmonary isthmus ablation with EEPVI has no obvious effects on AF recurrence.

Safety and Efficacy of Underdosing Non-vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Some patients with atrial fibrillation (AF) received underdoses of non-vitamin K antagonist oral anticoagulants (NOACs) in the real world. Underdosing is defined as administration of a dose lower than the manufacturer recommended dose. OBJECTIVES: To identify the efficacy and safety of underdosing NOACs as perioperative anticoagulation for atrial fibrillation ablation. METHODS: We retrospectively analyzed patients who received rivaroxaban or dabigatran etexilate according to dosage: adjusted low dosage (reduced by disturbed renal function; n = 30), underdosage (n = 307), or standard dosage (n = 683). Non-vitamin K antagonist oral anticoagulants and dosing decisions were at the discretion of treating cardiologists. RESULTS: Patients who received underdosed NOACs were older, more often female, and had lower body weight and lower renal function than those who received standard dosages. Activated clotting time at baseline in patients who received adjusted low dosage or underdosages was slightly longer than that in patients receiving standard dosages (156 ± 23, 151 ± 224, and 147 ± 24 seconds, respectively). Meaningful differences were not observed in other coagulation parameters. Adjusted low-, under-, and standard-dosing regimens did not differ in perioperative thromboembolic complications (0/30, 0.0%; 1/307, 0.3%; and 0/683, 0%, respectively) or major (0/30, 0.0%; 2/307, 0.6%; 3/683, 0.4%) and minor (1/30, 3.3%; 13/307, 4.2%; 25/683, 3.6%) bleeding episodes. When comparisons were performed for each NOAC, similar results were observed. CONCLUSIONS: With consideration of patient condition, age, sex, body weight, body mass index, and renal function, underdosing NOACs was effective and safe as a perioperative anticoagulation therapy for atrial fibrillation ablation. The therapeutic range of NOACs is potentially wider than manufacturer recommendations.

A rapid and precise method for measuring plasma apoE-rich HDL using polyethylene glycol and cation-exchange chromatography: a pilot study on the clinical significance of apoE-rich HDL measurements.

BACKGROUND: High-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents only a small portion of plasma HDL. Reliable methods for determining and isolating apoE-rich HDL have not been well studied. METHODS: We established a novel analytical method for apoE-rich HDL using polyethylene glycol and a cation-exchange column (PEG-column method). Furthermore, we examined biochemical correlates of apoE-rich HDL-cholesterol (HDL-C) in 36 patients who underwent coronary computed tomographic angiography. RESULTS: Our PEG-column method demonstrated high reproducibility (coefficient of variation <3.52%) and linearity up to 15mg/dl for apoE-rich HDL-C concentrations. Isolated apoE-rich HDL exhibited a larger diameter (14.8nm) than apoE-poor HDL (10.8nm) and contained both apoE and apoA-I. ApoE-rich HDL-C concentrations correlated significantly with triglycerides (rs=-0.646), LDL size (rs=0.472), adiponectin (rs=0.476), and other lipoprotein components. No significant correlation was obtained with the coronary calcium score. Multiple regression analysis revealed that plasma triglycerides and adiponectin concentrations remained significant independent predictors of apoE-rich (adjusted R2=0.486) but not apoE-poor HDL-C. CONCLUSIONS: The PEG-column method demonstrated, to various degrees, significant correlations between HDL subfractions and several lipid-related biomarkers involved in an atherogenic lipoprotein profile. Our separation technique for apoE-rich HDL is useful to clarify the role of apoE-rich HDL in atherosclerosis.

Adequate Initial Heparin Dosage for Atrial Fibrillation Ablation in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants.

BACKGROUND AND OBJECTIVE: During atrial fibrillation ablation, heparin is required and is guided by the activated clotting time (ACT). Differences in the ACT before ablation and adequate initial heparin dosing in patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) were examined. METHODS: Patients who received warfarin (control, N = 90), dabigatran etexilate (N = 90), rivaroxaban (N = 90) and apixaban (N = 90) were studied. A 100 U/kg dose of heparin was administered as a reliable control dose for warfarin, and the remaining patients were randomly administered 110, 120 or 130 U/kg of heparin in each NOAC group, followed by a continuous heparin infusion. RESULTS: Periprocedural thromboembolic and major bleeding were not observed. Minor bleeding occurred rarely without significant differences among the groups examined. Baseline ACTs were longer in the warfarin (152 ± 16 s) and dabigatran (153 ± 13 s) groups than in the rivaroxaban (134 ± 13 s) and apixaban (133 ± 20 s) groups. The initial bolus heparin dosages required to produce an ACT 15 min after the initial bolus that was identical to the control (333 ± 32 s) were 120 U/kg (318 ± 29 s) and 130 U/kg (339 ± 43 s) for dabigatran, 130 U/kg (314 ± 31 s) for rivaroxaban and 130 U/kg (317 ± 39 s) for apixaban. The NOAC groups required significantly larger doses of total heparin than the warfarin group. CONCLUSION: The baseline ACTs differed among the three NOAC groups. The results of the comparison with warfarin (the control) indicated that dosages of 120 or 130 U/kg for dabigatran, and 130 U/kg for rivaroxaban and apixaban, were adequate initial heparin dosages.

Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3ß under Oxidative Stress.

Eosinophil cationic protein (ECP) is well known as a cationic protein contained in the basic granules of activated eosinophils. Recent studies have reported that ECP exhibits novel activities on various types of cells, including rat neonatal cardiomyocytes. Here we evaluated the effects of ECP on rat cardiac myoblast H9c2 cells. Our results showed that ECP enhanced the survival of the cells, in part by promoting the ERK and Akt/GSK-3ß signaling pathways. ECP attenuated the cytotoxic effects of H2O2 on H9c2 cells as well as the production of reactive oxygen species, the number of apoptotic cells and caspase 3/7 activity in the cells. In conclusion, ECP activated the ERK and Akt/GSK-3ß pathways, resulting in anti-oxidative effects on H9c2 cells that attenuated apoptosis.

Arterial stiffness determined according to the cardio-ankle vascular index is associated with paroxysmal atrial fibrillation: a cross-sectional study.

BACKGROUND: Several lines of evidence suggest that atrial fibrillation (AF) may be a consequence of vascular disease. We investigated the relationship between cardio-ankle vascular index (CAVI), a new index of arterial stiffness, and the presence of paroxysmal AF (PAF). METHODS AND RESULTS: 181 outpatients (91 patients with PAF and 90 age- and gender-matched subjects without PAF) were analysed for their sinus rhythm. The CAVI was significantly higher in patients with PAF than in subjects without PAF (9.0±1.0 vs 8.7±0.8, p<0.01). In all subjects, the CAVI was significantly correlated with the left ventricular mass index (r=0.30, p<0.01), left atrial diameter (r=0.22, p<0.01), and augmentation index, a parameter of wave reflection (r=0.32, p<0.01), in addition to age, systolic blood pressure and pulse pressure. Logistic analysis demonstrated that the CAVI was independently associated with PAF even after adjustment for confounding factors. The adjusted OR of PAF was 1.8 for each unit increase in the CAVI (p=0.01). CONCLUSIONS: Our finding suggests that increased arterial stiffness may be involved in the maintenance of AF.

Neointimal calcification after stenting and chronic kidney disease.

The timing and incidence of neointimal calcification after stenting (NIC) is largely unknown. The purpose of our study was to elucidate the characteristics of NIC. The presence of NIC in patients who underwent intravascular ultrasound between June 30, 2009 and June 30, 2012 was analyzed. The patients were divided into two groups based on the follow-up period: < 365 days or ≥ 365 days. A total of 181 images were analyzed. Those with NIC had a lower estimated glomerular filtration rate [51 (6-60) versus 61 (52-72) mL/minute/1.73 m²; P < 0.01] and longer time after stenting [3198 (1710-3684) versus 211 (180-516) days; P < 0.01] compared to those without NIC. NIC during short-term follow-up was observed only in patients who were on hemodialysis. On the other hand, NIC in the long-term follow-up was observed only in patients with bare metal stents. The development of NIC was related to renal function and time after stenting. NIC in the short-term and the long-term follow-up was observed only in patients who were on hemodialysis and who were implanted with a bare metal stent, respectively.

A case report of acute myocardial infarction induced by coronary spasm. Intravascular findings.

A 53-year-old male complaining of chest pain was admitted to our hospital with suspected acute myocardial infarction (AMI). Emergent coronary angiography (CAG) determined a totally occluded middle right coronary artery (RCA). Thrombus aspiration was conducted, followed by intravascular ultrasound (IVUS) imaging. Diffuse intima plus media thickness was identified at the obstruction site and a thrombus was observed proximally to the occlusion site on IVUS. Following isosorbide dinitrate (ISDN) administration, dilatation of the RCA was confirmed. IVUS study indicated the luminal dilatation was achieved by the release of the diffuse intima plus media thickening. Of note, plaque volume showed no significant difference after administration of ISDN at any vessel site. These results clearly show that luminal dilatation and vessel dilatation were achieved from the redistribution of plaque volume (intima plus media). A follow-up CAG showed no significant stenosis in the RCA. After a provocation test using methylergometrine maleate, the RCA was totally occluded at the very site of the initial event. The involvement of vasospasm as a cause of AMI in the present case was doubly confirmed with characteristic IVUS images of vasospasm in the acute phase and with a provocation test at follow-up.

Reduced diurnal variation of heart rate is associated with increased plasma B-type natriuretic peptide level in patients with atrial fibrillation.

BACKGROUND: The plasma B-type natriuretic peptide (BNP) level has been shown to be increased in patients with chronic atrial fibrillation (AF) independent of left ventricular ejection fraction (LVEF). The purpose of this study is to evaluate the relationship between the plasma BNP level and heart rate variation in patients with AF. HYPOTHESIS: The plasma BNP level is associated with heart rate variation in patients with AF. METHODS: A total of 102 patients with AF and preserved LVEF were included from 2 hospitals. The ambulatory electrocardiographic recording and measurement of plasma BNP levels were performed simultaneously. Echo-Doppler parameters were measured as the average of 10 consecutive cardiac cycles. RESULTS: A difference in the mean heart rate between night and day (DIFF) and the standard deviation of the 5-miniute mean R-R interval (SDARR) were significantly associated with log-transformed BNP levels (r = -0.411, P < 0.001 and r = -0.243, P = 0.049, respectively). In echocardiography, the ratio of E velocity to early diastolic velocity, which reflects left ventricular (LV) filling pressure, was significantly correlated with the DIFF and SDARR, along with the log-transformed BNP level. Stepwise multiple linear regression analysis revealed that the DIFF and age were independent factors related with the BNP level (P < 0.01). CONCLUSIONS: The reduced diurnal variation of heart rate was significantly associated with increased BNP, which is linked to LV diastolic dysfunction in patients with AF.

Usefulness of dabigatran etexilate as periprocedural anticoagulation therapy for atrial fibrillation ablation.

BACKGROUND: The usefulness of dabigatran etexilate for the prevention of stroke in patients with atrial fibrillation (AF) has been reported. OBJECTIVES: In this study the efficacy and safety of dabigatran etexilate for anticoagulation for AF ablation were examined. METHOD: Patients were divided into three groups: Group 1, interrupted warfarin bridged by heparin between pre- and post-ablation; Group 2, continuous warfarin therapy; and Group 3, dabigatran etexilate therapy. Anticoagulation therapy with warfarin or dabigatran etexilate was performed from 30 days before to at least 90 days after AF ablation. Dabigatran etexilate was administered at 110 or 150 mg twice daily, depending on renal function and age. RESULTS: Patients' clinical characteristics, associated disorders, echocardiographic parameters and arrhythmia status were not different among the three groups. Procedural parameters such as procedural time and radiofrequency energy supply were also not different among the three groups. The dabigatran etexilate group and the warfarin groups had no embolic complications (stroke, cerebral transient ischaemic attack, deep venous thrombosis or pulmonary embolism). No pericardial tamponade was observed in the dabigatran etexilate group, while two patients in each of Group 1 (2/194, 1.0 %) and Group 2 (2/203, 0.98 %) developed cardiac tamponade, though the differences were not significant. Pericardial effusion and groin haematoma were observed in one patient each (1/105, 0.9 %) in the dabigatran etexilate group, and the incidences were not different from the warfarin group (Group 1: 4/194, 2.1 % and 2/194, 1.0 %; Group 2: 3/203, 1.5 % and 2/203, 1.0 %, respectively). As a whole, the safety outcomes did not differ among the three groups. CONCLUSION: Dabigatran etexilate is an effective and safe anticoagulation therapy for AF ablation. Thus, dabigatran etexilate appears to be useful as an alternative anticoagulant therapy to warfarin for AF ablation.