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Aim: During percutaneous coronary intervention (PCI), complicated lesions in the target coronary artery often hinder device delivery. Fluid lubricants have commonly been used to reduce friction between adjacent solid materials in manufacturing, thus achieving smoother action. This ex vivo experimental study examined whether a contrast medium could function as a fluid lubricant during PCI., Methods and Results: We used two different coronary artery lesion models with distinct complexities made from silicon. Each model was fit into the ex vivo PCI-simulation system. This ex vivo laboratory equipment consisted of ordinary PCI instruments and an aorta model from the Valsalva sinus to the descending aorta. A Wolverine™ cutting balloon catheter was advanced through each lesion model via a guide catheter set into the system. The maximum force required to push the catheter through the lesion models was measured while the vessel system was filled with either normal saline or contrast medium. The maximum force required was significantly lower with the contrast medium (1.38 ± 0.21 N in the normal-saline condition vs. 0.92 ± 0.05 N in the contrast-medium condition in the lesion model A, p < 0.001; 1.30 ± 0.07 N in the normal-saline condition vs. 1.14 ± 0.04 N in the contrast-medium condition in the lesion model B, p < 0.001)., Conclusions: The contrast medium for vessel system filling reduced the force required to push the devices through the lesion models. This contrast medium represents a potential candidate for a liquid lubricant to facilitate device delivery for complicated coronary lesions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: The relationship between left ventricular diastolic dysfunction (LVDD) and paroxysmal atrial fibrillation (PAF) remains unclear because of a lack of standard measures to evaluate LVDD. Accordingly, we examined the association between the prevalence of PAF and each LVDD grade determined according to the latest American Society of Echocardiography guidelines. Methods and Results: In all, 2,063 patients without persistent AF who underwent echocardiography at Saitama Municipal Hospital from July 2016 to June 2017 were included in the study. Patients were divided into LVDD 6 categories: No-LVDD (n=1,107), Borderline (n=392), Grade 1 (n=204), Indeterminate (n=62), Grade 2 (n=254), and Grade 3 (n=44). PAF was documented in 111 (10.0%), 81 (20.7%), 28 (13.7%), 6 (9.7%), 52 (20.5%), and 24 (54.5%) patients in the No-LVDD, Borderline, Grade 1, Indeterminate, Grade 2, and Grade 3 categories, respectively. PAF prevalence was higher in patients with Grade 3 LVDD across the whole study population. Subgroup analyses showed that the prevalence of PAF increased with increased LVDD grade in patients with reduced left ventricular ejection fraction. This relationship was significant in multivariate analysis including various patient characteristics. Conclusions: LVDD severity determined on the basis of the latest echocardiographic criteria was associated with the prevalence of PAF. The present findings shed light on the development of new therapeutic markers for PAF., Competing Interests: The authors declare that there are no conflicts of interest. This work has no relationship with industry., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Background: Gastric endoscopic submucosal dissection (ESD) has gradually come to be recommended as the optimal treatment for early gastric cancer; however, one of the primary issues is postoperative bleeding. Although second-look endoscopy is conventionally performed to reduce the risk of postoperative bleeding, its benefit has not yet been clearly elucidated. The objective of this study was to elucidate the benefit of second-look endoscopy., Methods: A total of 459 lesions in patients were underwent gastric ESD from May 2004 to April 2013 at our hospital were included in the analysis. The patients were divided into those who had bleeding within 24 hours after ESD (immediate bleeding) and those in whom bleeding occurred 24 hours or more after the procedure (delayed bleeding); the underlying disease, age, lesion site, diameter of the resected specimen, and lesion diameter were analyzed to identify the risk factors for postoperative bleeding after ESD., Results: Post-ESD immediate or delayed bleeding occurred in 23 of the 459 cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%) excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases (53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the 210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant difference between the two groups. Overall, the following factors were identified as the risk factors for postoperative bleeding: young age (P = 0.005), lesions in the L segment (P = 0.042), and large size of the resected specimen (P = 0.005). The risk factors identified in the immediate bleeding group were lesions in the L segment (P = 0.032), large size of the resected specimen (P < 0.001), and large tumor size (P = 0.011), and those in the delayed bleeding group were young age (P = 0.013) and concomitant renal disease (P = 0.011)., Conclusions: The results of this study suggest that second-look endoscopy after gastric ESD may not be useful for preventing postoperative bleeding.

We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine. She was started on adefovir (10 mg daily) while still continuing lamivudine therapy. Four mo later her liver function improved and serum Hepatitis B virus (HBV)-DNA level became undetectable. Three years after the start of additional adefovir treatment, hepatocellular carcinoma (HCC) was detected and the patient underwent a successful hepatectomy. Our findings suggest that the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis, but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis, allowing HCC surgery.

Background: The serum levels of soluble elastin increase in patients with aortic dissection, but its distribution and characteristics are unclear., Methods and Results: The 173 aortic specimens were categorized into 4 groups under microscopy (non-atherosclerotic aorta, n=13; fiber-rich plaque, n=77; lipid-rich plaque, n=66; ruptured plaque, n=17). Soluble elastin was abundant within the intima of both the non-atherosclerotic aorta and fiber-rich plaque, rather than in the media, and was decreased within the intima of lipid-rich and ruptured plaques. Soluble elastin levels decreased with progress of atherosclerosis (6.0 +/-0.3 microg/mg protein in non-atherosclerotic aorta; 5.8 +/-0.2 microg/mg protein in fiber-rich plaque; 4.9 +/-0.2 microg/mg protein in lipid-rich plaque; 2.8 +/-0.4 microg/mg protein in ruptured plaque, P<0.05). As well, both matrix metalloprotease-9 activity and elastin mRNA expression showed inverse distribution against soluble elastin (r=0.437, P<0.0001; r=0.186, P<0.05, respectively). Multivariable analysis revealed a decrease in the level of soluble elastin in ruptured plaque (2.8 +/-0.4 microg/mg protein in ruptured plaque, n=18; 5.5 +/-0.2 microg/mg protein in non-ruptured plaque, n=155, P<0.01). Furthermore, western blot showed soluble elastin consists of heterogeneous molecular pattern proteins., Conclusions: Both the synthesis and degradation of elastin may be enhanced in active atherosclerotic lesions.

Objectives: To examine the effects of coronary artery vasodilators on coronary arterial distensibility using intravascular coronary ultrasound (IVUS)., Background: There is limited information on the effect of coronary artery vasodilators on coronary arterial distensibility., Methods: We studied 20 patients using IVUS. Patients received 100 microg of nitroglycerin (10 patients) or 1 mg of verapamil (10 patients) intravenously. We measured coronary arterial elasticity, the distensibility index, compliance and stiffness index. There were no differences in patient characteristics, lesion characteristics or baseline coronary arterial distensibility between the two groups., Results: Systolic and diastolic blood pressure decreased in both groups (p < 0.05). Maximal coronary arterial cross-sectional luminal area (LA) during the cardiac cycle showed similar dilation in both groups. Nitroglycerin increased maximal LA by 5%, and verapamil increased it by 4% (p < 0.05; p < 0.0001, respectively). However, the degree of dilation of the minimal LA during the cardiac cycle showed a different pattern. Nitroglycerin dilated the minimal LA by 8%, while verapamil dilated the minimal LA by 2% (p < 0.001, p < 0.05, respectively). Consequently, the degree of expansion of LA during each cardiac cycle increased in the verapamil group and decreased in the nitroglycerin group. Thus, nitroglycerin decreased elasticity by 31% (p < 0.001), with no change in compliance, stiffness index or distensibility index. While, verapamil increased elasticity by 37%, the distensibility index by 48% and compliance by 53%, and decreased the stiffness index by 27% (all, p < 0.0001)., Conclusions: While both drugs acutely dilate the coronary arteries, nitroglycerin reduced local coronary arterial distensibility; however, verapamil increased local coronary arterial distensibility.

This study was investigated the role that endothelial function and systemic vascular resistance (SVR) play in determining cardiac function reserve during exercise by a new ambulatory radionuclide monitoring system (VEST) in patients with heart disease. The study population consisted of 32 patients. The patients had cardiopulmonary stress testing using the treadmill Ramp protocol and the VEST. The anaerobic threshold (AT) was autodetermined using the V-slope method. The SVR was calculated by determining the mean blood pressure/cardiac output. Flow-mediated vasodilation (FMD) was measured in the brachial artery to evaluate endotheilial function. FMD and the percent change f'rom rest to AT in SVR correlated with those from rest to AT in ejection fraction and peak ejection ratio by VEST, respectively. Our findings suggest that FMD in the brachial artery and the SVR determined by VEST in patients with heart disease can possibly reflect cardiac function reserve during aerobic exercise.

Background: Accurate assessment of aortic valve area (AVA) is important for clinical decision-making in patients with aortic valve stenosis (AS). The role of three-dimensional echocardiography (3D) in the quantitative assessment of AS has not been evaluated so far., Objectives: To evaluate the reproducibility and accuracy of real-time three-dimensional echocardiography (RT3D) and 3D-guided two-dimensional planimetry (3D/2D) for assessment of AS, and compare these results with those of standard echocardiography and cardiac catheterisation (Cath)., Methods: AVA was estimated by transthoracic echo-Doppler (TTE) and by direct planimetry using transoesophageal echocardiography (TEE) as well as RT3D and 3D/2D. 15 patients underwent assessment of AS by Cath., Results: 33 patients with AS were studied (20 men, mean (SD) age 70 (14) years). Bland-Altman analysis showed good agreement and small absolute differences in AVA between all planimetric methods (RT3D vs 3D/2D: -0.01 (0.15) cm(2); 3D/2D vs TEE: 0.05 (0.22) cm(2); RT3D vs TEE: 0.06 (0.26) cm(2)). The agreement between AVA assessment by 2D-TTE and planimetry was -0.01 (0.20) cm(2) for 3D/2D; 0.00 (0.15) cm(2) for RT3D; and -0.05 (0.30) cm(2) for TEE. Correlation coefficient r for AVA assessment between each of 3D/2D, RT3D, TEE planimetry and Cath was 0.81, 0.86 and 0.71, respectively. The intraobserver variability was similar for all methods, but interobserver variability was better for 3D techniques than for TEE (p<0.05)., Conclusions: The 3D echo methods for planimetry of the AVA showed good agreement with the standard TEE technique and flow-derived methods. Compared with AV planimetry by TEE, both 3D methods were at least as good as TEE and had better reproducibility. 3D aortic valve planimetry is a novel non-invasive technique, which provides an accurate and reliable quantitative assessment of AS.

A young woman presented with takotsubo cardiomyopathy after a syncopal attack caused by torsades de pointes. Two-dimensional echocardiography on admission showed left ventricular apical akinesis (ballooning) and basal hyperkinesis, compatible with takotsubo cardiomyopathy. This gradually normalized in 2 months. ECG on admission showed remarkable QT prolongation, U waves, and negative T waves, which also gradually normalized. Coronary angiography revealed no organic stenosis; however, acetylcholine provocation test caused the QT interval to again become prolonged. During treadmill exercise stress testing, the QT interval shortened as heart rate increased. Therefore, without genetic analysis, this patient was considered to have sporadic long QT syndrome in which takotsubo cardiomyopathy developed after the syncopal attack caused by torsades de pointes.

Objectives: We evaluated the potential vasodilator effects of transcutaneous low-frequency ultrasound (US) in human brachial arteries., Background: Recent data show that transthoracic low-frequency US energy results in canine coronary artery vasodilation., Methods: Brachial artery diameters were measured before and after low-frequency US (29 kHz, 1.4 W/cm2) exposure using US imaging with a linear-array transducer. We assessed the time course of diameter changes after US in 20 subjects. In 10 of 20 subjects, brachial artery flow-mediated vasodilation (FMD) was measured to compare the effect of US to a standard method of evaluating endothelial function., Results: Significant vasodilation was seen after 2 min of US compared with baseline values. At 5 min of US, the brachial artery diameter increased by 4.1%. In addition, the arteries continued to dilate after US exposure. At 3 min after US there was a 5.4%, and at 5 min after US a 6.0% increase in vessel diameter (p < 0.001). These diameters returned to baseline dimensions about 20 min after stopping US. Ultrasound-mediated vasodilation and percentage FMD showed good correlation (r = 0.87; p < 0.001)., Conclusions: This is the first study to demonstrate that noninvasive transcutaneous low-frequency US energy dilates human brachial arteries. This arterial vasodilator effect has a rapid onset (within 2 min), lasts about 20 min, and is similar in magnitude to that of FMD. The vasodilator effect of US may have diagnostic and therapeutic potential in patients with or at risk for vascular disease.

Background: Vasodilator response to acetylcholine (ACh) (ie, endothelium-dependent dilation) is impaired in the peripheral and coronary circulation of patients with coronary risk factors and coronary artery disease (CAD). There is a close relationship of vasodilator response to ACh in both the coronary artery (CA) and the brachial artery (BA), but the comparative prognostic importance of these responses has not been fully investigated in relatively low-risk suspected CAD., Methods and Results: The flow responses of both the CA and BA were measured in 70 patients with suspected CAD, excluding patients with triple-vessel disease and known peripheral or cerebrovascular disorders. A Doppler guidewire was placed into a major branch of the CA and a proximal portion of the left BA. ACh was infused at 10(-8), 10(-7) and 10(-6) mol/L for 3 min into the CA and at 7.5, 15, and 30 mug/min for 5 min into BA. The flow response was obtained by multiplying the average peak velocity by the cross-sectional area from quantitative angiography. Vasodilator response to ACh was assessed by the ratio of ACh-induced flow/baseline flow, expressed as coronary blood flow index (CBFI) or brachial blood flow index (BBFI). There were 39 CAD patients (61 +/- 8 years old) and 31 normal coronary patients (NL, 58 +/- 11 years old) who were followed up for 53 +/- 17 months. Eleven patients had coronary events (CE) during this period: 1 case of nonfatal myocardial infarction and 10 cases of unstable angina. A strong correlation between CBFI and BBFI was observed at middle-and high-doses of ACh (r=0.72, p<0.0001, 15 microg/min vs 10(-7) mol/L; r=0.76, p<0.0001, 30 microg/min vs 10(-6) mol/L). Kaplan-Meier analysis, using the best cut-off values obtained from receiver-operating characteristic curves for CE, revealed that both CBFI and CAFI were significant predictors for CE., Conclusions: The BA vasodilator response to optimal ACh dosage can be used as a surrogate prognostic predictor for coronary endothelial function tests in patients with suspected CAD.

Background: Chronic mental and physical stress has been suggested to be a trigger for cardiovascular events. In addition, a reduction in levels of intracellular magnesium has been reported to cause vasoconstriction while enhancing platelet-dependent thrombosis., Hypothesis: The purpose of this study was to investigate whether chronic stress affects endothelial function and intracellular magnesium levels in humans., Methods: Flow-mediated dilation (endothelium-dependent vasodilation) and sublingual nitroglycerin-induced dilation (0.3 mg, endothelium-independent vasodilation) were measured in the brachial artery in 30 healthy male college students, aged 22 +/- 1 years, using high-resolution ultrasound both before and immediately after a 4-week final term examination period. Erythrocyte magnesium concentration was measured simultaneously. All students had chronic sleep deprivation for 4 weeks, during which sleep lasted < 80% of that on ordinary days; in addition, the students were under great stress to pass the examination. This condition was considered to be chronic stress., Results: Chronic stress decreased flow-mediated dilation and erythrocyte magnesium concentration (from 7.4 +/- 3.0 to 3.7 +/- 2.3%, p < 0.05; from 5.7 +/- 0.4 to 5.5 +/- 0.4 mg/ml, p < 0.05, respectively). The change in flow-mediated dilation correlated significantly with that of the erythrocyte magnesium concentration (r = 0.43, p < 0.05), but not with nitroglycerin-induced dilation., Conclusions: Chronic stress was found to attenuate endothelial function, which may also be associated with a reduction in the intracellular magnesium level in humans.

Objectives: We examined whether preinterventional arterial remodeling influenced the interventional results after stenting., Background: Arterial remodeling is seen in atherosclerotic lesions, and it may play an important role in the early stage of atherosclerosis., Methods: We examined 113 lesions that underwent elective stenting using tubular slotted stents under intravascular ultrasound guidance. The lesions were divided into three groups--adequate, intermediate and inadequate remodeling group--according to preinterventional arterial remodeling. The patients were subjected to coronary angiography and intravascular ultrasound evaluation on average 6.4 months after stenting., Results: At baseline and immediately after stenting, there were no differences in quantitative angiographic analysis among remodeling groups. However, the plaque cross-sectional area (CSA) in the minimal lumen CSA at preintervention and intimal hyperplasia CSA at follow-up were significantly larger in the adequate remodeling group than in the inadequate remodeling group. The restenosis rate of stenting for the lesions with inadequate arterial remodeling was very low (9.4%). A significant positive correlation was found between preinterventional plaque CSA and intimal hyperplasia CSA at follow-up (r = 0.47, p < 0.0001). Moreover, remodeling index significantly correlated with relative intimal hyperplasia CSA (r = 0.28, p < 0.01)., Conclusions: Preinterventional arterial remodeling influenced the development of intimal hyperplasia after stenting.

Background: Paradoxical peripheral vasodilation is one of the suspected mechanisms of neurally mediated syncope. Parasympathetic stimulation following sympathetic activation during orthostatic stress mainly contributes to this vasodilation., Hypothesis: Since endothelial function modulates peripheral vascular tone, this study aimed to determine whether endothelial function and inappropriate peripheral vasomotion has a significant role in the pathogenesis of neurally mediated syncope., Methods: To investigate whether endothelial function is augmented or whether abnormal peripheral vasomotion exits, flow-mediated dilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl trinitrate-induced dilation (0.3 mg, GTN-D, endothelium-independent vasodilation) were measured in the brachial artery in 16 patients with neurally mediated syncope, aged 33 +/- 10 years, by using high-resolution ultrasound. All patients underwent positive head-up tilt testing. These measures were compared with those in 16 control subjects matched with the patients by age, gender, and coronary risk factors. For FMD, percent diameter changes were obtained from baseline to hyperemic conditions (1 min after 5 min occlusion of the forearm artery). There were five smokers in both the patient and the control groups, but there was no structural heart disease in either group., Results: Baseline brachial artery diameters were comparable (3.8 +/- 0.6 vs. 3.8 +/- 0.7 mm, NS). Flow-mediated dilation in patients with neurally mediated syncope had a normal value of 9.8 +/- 5.0% despite the inclusion of five smokers. Flow-mediated dilation and GTN-D in patients with neurally mediated syncope were significantly greater than those in controls (9.0 +/- 5.0 vs. 3.0 +/- 3.5%, p<0.05; 18.4 +/- 5.5 vs. 14.1 +/- 4.4%, p<0.05)., Conclusions: Augmented endothelial function and/or abnormal peripheral vasomotion in peripheral arteries are important in patients with neurally mediated syncope in selected populations.

Background and Hypothesis: Brachial artery flow-mediated dilation (FMD), a noninvasive, widely used clinical index of endothelial function and magnitude of FMD, has been reported to be closely related to many coronary risk factors and coronary atherosclerosis. However, there has been no study that examines the diurnal change of FMD. We designed this study to reveal the diurnal variation of FMD in healthy volunteers., Methods: We examined FMD in response to reactive hyperemia by high resolution ultrasound in 13 healthy young men (age 25-32) at four different times over the course of a day., Results: Mean measures of brachial artery FMD was 4.0% at 8:00, 5.3% at 12:00, 9.7% at 17:00, and 6.9% at 21:00 hours. Flow-mediated dilation at 8:00 and at 12:00 hours was significantly lower than that at 17:00 (p < 0.05)., Conclusions: These results show that endothelial function has diurnal variation and is significantly attenuated in the morning. Morning attenuation of endothelial function should be recognized in clinical research and may play an important role in the circadian variation of the occurrence of acute cardiovascular events.