Gastrointestinal Bleeding During Direct Oral Anticoagulant Therapy in Patients With Nonvalvular Atrial Fibrillation and Risk of Polypharmacy.

Although concomitant medications have been raised as a factor affecting hemorrhage during direct oral anticoagulant (DOAC) therapy, details remain unelucidated. This study was conducted to clarify the relationship between concomitant medications with possible pharmacokinetic interactions and number of concomitant medications, and bleeding and embolism in patients with nonvalvular atrial fibrillation on DOACs. The subjects were 1010 patients prescribed DOACs from a single-center at the Teikyo University Hospital between April 2011 and June 2018. This study was an exploratory analysis and investigated their course between the first prescription and December 2018, including the presence or absence of clinically relevant bleeding, gastrointestinal bleeding, and major cardiovascular and cerebrovascular events. Impacts of medications were evaluated by the general linear model with inverse probability-weighted propensity score. The observation period was 2272 patient-years. The rate of bleeding was 4.7%/year, gastrointestinal bleeding was 2.8%/year, and major cardiovascular and cerebrovascular events were 2.0%/year. Taking 10 or more oral medications concurrently was a significant risk for gastrointestinal bleeding (hazard ratio, 2.046 [95%CI, 1.188-3.526]; P = .010). Nonsteroidal anti-inflammatory drugs were the only significant risk for gastrointestinal bleeding. Clinicians should be aware of gastrointestinal bleeding when using DOACs with patients taking more than 10 medications and/or nonsteroidal anti-inflammatory drugs.

Clinical factors associated with safety and efficacy in patients receiving direct oral anticoagulants for non-valvular atrial fibrillation.

Although patients suffering from atrial fibrillation have increased worldwide, detailed information about factors associated with bleeding during direct oral anticoagulant therapy remains insufficient. We studied 1086 patients for whom direct oral anticoagulants were initiated for non-valvular atrial fibrillation between April 2011 and June 2017. Endpoints were clinically relevant bleeding or major adverse cardiac and cerebrovascular events until the end of December 2018. Incidences of bleeding and thrombosis were 4.5 per 100 person-years and 4.7 per 100 person-years, respectively. Most bleeding events represented gastrointestinal bleeding. Multivariate analysis revealed initiation of anticoagulants at ≥ 85 years old as significantly associated with bleeding, particularly gastrointestinal bleeding, but not major cardiac and cerebrovascular events. Other significant factors included chronic kidney disease, low-dose aspirin and nonsteroidal anti-inflammatory drugs. For gastrointestinal bleeding alone, histories of gastrointestinal bleeding and malignancy also showed positive correlations, in addition to the above-mentioned factors. Clinicians should pay greater attention to the risk of gastrointestinal bleeding when considering prescription of anticoagulants to patients ≥ 85 years old with atrial fibrillation.

Prevalence and Predictors of Atherosclerotic Peripheral Arterial Obstructive Disease in Severe Heart Valve Diseases.

Despite witnessing an upsurge in heart valve diseases (HVDs), the correlation between HVDs and atherosclerotic peripheral arterial obstructive disease (PAOD) remains unclear. This study aims to investigate the prevalence and predictors of PAOD in HVDs.In this study, a total of 245 consecutive patients were examined: 153 with severe aortic valve stenosis (AS), 66 with severe primary mitral valve regurgitation (MR), and 26 with severe pure native aortic valve regurgitation (AR). All patients underwent ultrasound scan of the carotid artery to ascertain the presence of internal carotid artery stenosis (ICAS). ICAS was defined as a peak systolic velocity ≥ 125 cm/second and/or ≥ 50% reduction in diameter. In addition, we measured the ankle-brachial index in each leg using a volume plethysmograph. A result of ≤ 0.9 was considered lower extremity artery disease (LEAD).The presence of ICAS was statistically more frequent in patients with severe AS than in patients with severe MR and AR (11.1% versus 1.5% versus 3.8%; P = 0.038). LEAD was present in patients with severe AS (17.6%) and MR (10.6%) but not in patients with severe AR (P = 0.037). The multivariate analysis revealed that the presence of severe AS (OR, 5.6 [1.3-24.9]; P = 0.023) was an independent predictor for ICAS, while history of coronary artery disease (OR, 4.8 [2.2-10.5]; P < 0.001) was an independent predictor for LEAD.The prevalence of PAOD varies depending on each valvular disease. Individual screening should be considered on the basis of atherosclerotic risk factors, especially for patients with severe AS.

Incidence, Predictors, and Midterm Clinical Outcomes of Myocardial Injury After Transcatheter Aortic-Valve Implantation.

Our aim was to assess the clinical effects of myocardial injury after transcatheter aortic-valve implantation (TAVI). Between October 2013 and July 2016, 157 patients underwent TAVI with Sapien XT, Sapien 3, or CoreValve prostheses at our institute. Of these, 130 patients for whom the transapical approach was not used were included in this study. Myocardial injury was defined as a peak troponin I level of ≥1.5 ng/mL within 48 hours after TAVI. We evaluated the predictors of myocardial injury and compared the clinical outcomes of 82 patients classified as the myocardial injury group and 44 patients classified as the non-myocardial injury group. The patients were aged 85 ± 6 years. Myocardial injury occurred in 82 patients (65.1%). Age (per 1 increase) (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, P = 0.041), female sex (OR: 3.88, 95% CI: 1.23-12.22, P = 0.021), valve type (Sapien XT; OR: 4.22, 95% CI: 1.15-15.47, P = 0.03, Core valve; OR: 18.12, 95% CI: 2.86-114.59, P = 0.002), balloon aortic valvuloplasty as a bridge therapy (OR: 0.10, 95% CI: 0.02-0.42, P = 0.002), and left ventricular end-diastolic volume (LVEDV) (per 1 increase) (OR: 0.97, 95% CI: 0.95-0.99, P = 0.003) were associated with myocardial injury in a multivariate model. The myocardial injury group did not have a higher rate of midterm (365-day) mortality (log-rank test P = 0.57) than the non-myocardial injury group on Kaplan-Meier analysis. Myocardial injury after TAVI was not associated with midterm mortality.

Efficacy and safety of transcatheter aortic valve implantation with Edwards SAPIEN 3 and XT in smaller Asian anatomy.

We aimed to compare the efficacy and safety of transcatheter aortic valve implantation (TAVI) using Edwards SAPIEN 3 (S3) valve and SAPIEN XT) in smaller anatomy. The new generation S3 TAVI device has been used worldwide; however, its efficacy and safety in smaller Asian anatomy remain unknown. Between February 2014 and March 2017, 166 consecutive patients (S3, 54; XT, 112) were treated with balloon-expandable TAVI in a single center and their outcomes were analyzed. Median patient age was 85 (range: 81-88) years and mean body surface area was 1.41 ± 0.15 m2. A 23-mm size valve was used in S3 and XT groups (70 vs. 62%, p = 0.224). The transfemoral approach was more frequently used in the S3 than in the XT group (96 vs. 72%, p < 0.001). Although, the minimal luminal diameter of the femoral artery was smaller in the S3 group (5.9 vs. 6.4 mm, p = 0.001), the rates of major (2 vs. 11%, p = 0.226) and minor (11 vs. 5%, p = 0.107) vascular complications did not increase. The frequency of paravalvular leaks (PVL) ≥ 2 was significantly reduced in the S3 group (11 vs. 61%, p < 0.001); however, pre- (24 vs. 91%, p < 0.001) and post- (4 vs. 19%, p < 0.001) dilatations were less frequently performed. Pacemaker implantation incidence did not increase (4 vs. 5%, p = 1.0) and peak velocity of the transcatheter heart valve was significantly higher in the S3 group (2.3 vs. 2.2 m/s, p = 0.046). Device success was high (89 vs. 93%, p = 0.387) while the 30-day all-cause mortality was low (2 vs. 1%, p = 0.583) in both groups. TAVI with the S3 device was safe and effective, with low incidence of vascular complications and reduced PVL, in smaller body-sized Asians.

Development of new risk score for pre-test probability of obstructive coronary artery disease based on coronary CT angiography.

Existing methods to calculate pre-test probability of obstructive coronary artery disease (CAD) have been established using selected high-risk patients who were referred to conventional coronary angiography. The purpose of this study is to develop and validate our new method for pre-test probability of obstructive CAD using patients who underwent coronary CT angiography (CTA), which could be applicable to a wider range of patient population. Using consecutive 4137 patients with suspected CAD who underwent coronary CTA at our institution, a multivariate logistic regression model including clinical factors as covariates calculated the pre-test probability (K-score) of obstructive CAD determined by coronary CTA. The K-score was compared with the Duke clinical score using the area under the curve (AUC) for the receiver-operating characteristic curve. External validation was performed by an independent sample of 319 patients. The final model included eight significant predictors: age, gender, coronary risk factor (hypertension, diabetes mellitus, dyslipidemia, smoking), history of cerebral infarction, and chest symptom. The AUC of the K-score was significantly greater than that of the Duke clinical score for both derivation (0.736 vs. 0.699) and validation (0.714 vs. 0.688) data sets. Among patients who underwent coronary CTA, newly developed K-score had better pre-test prediction ability of obstructive CAD compared to Duke clinical score in Japanese population.

Impact of combined assessment of coronary artery calcium score, carotid artery plaque score, and brachial-ankle pulse wave velocity for early coronary revascularization in patients with suspected coronary artery disease.

Coronary artery calcium score (CACS) measured by multi-detector computed tomography, carotid plaque score (CPS) measured by carotid artery ultrasound, and brachial-ankle pulse wave velocity (baPWV) are noninvasive screening tools for coronary artery disease. The aim of this study was to determine whether the combination of CACS, CPS, and baPWV improves the prognostic value for future cardiac events. CACS, CPS, and baPWV were assessed in 77 patients (mean age, 65 years, 49 males) undergoing invasive coronary angiography. ECG-triggered MSCT was used to assess CACS. CPS was defined as the sum of all plaque heights in bilateral carotid arteries. The highest baPWV was used for analysis. Cardiac events were defined as cardiac death, nonfatal myocardial infarction, or coronary revascularization. Thirty-two cardiac events (41.6%) occurred during follow-up (23.6 ± 20.8 months), consisting of 28 PCIs and 4 CABGs. The best cutoff values of positive CACS, CPS, and baPWV for predicting cardiac events were ≥ 50, ≥ 5, and ≥1.6 m/second, respectively. For the combination of the 3 modalities, the positive test was defined as having at least 1 positive result by each method. The negative predictive value of all 3 modalities combined was better than that of CACS alone. The event-free rate was higher in patients with negative results for all 3 parameters compared with those that were positive (100% versus 44.8%, P < 0.0001). The prognostic value of using combined assessment of CACS, CPS, and baPWV is more effective for predicting cardiac events than CACS alone.

Angiographic and clinical outcomes of 100 consecutive severe calcified lesions requiring rotational atherectomy prior to sirolimus-eluting stent implantation in hemodialysis and non-hemodialysis patients.

Both severe calcified lesions and hemodialysis (HD) are predictors for high rates of restenosis, even in the drug-eluting stent era. We sought to investigate the angiographic and clinical outcome in a population of HD versus non-hemodialysis (non-HD) patients with severe calcified lesions requiring rotational atherectomy. One hundred consecutive lesions (28 lesions in the HD group, 72 in the non-HD group) from 82 patients (19 patients in the HD group, 63 in the non-HD group) requiring rotational atherectomy prior to sirolimus-eluting stent (SES) implantation were analyzed post-procedure and at 8 months. Clinical outcomes were assessed at 12 months. Inclusion criteria were calcified lesions with >270° of superficial calcification on the intravascular ultrasound (IVUS), lesions that the IVUS could not cross, or undilatable lesions. There were no differences in patient characteristics except for age. Although both baseline and post-procedure angiographic findings were similar between the two groups, late loss in stented segment was significantly greater in the HD group than in the non-HD group (HD vs. non-HD: 0.69 ± 0.74 mm vs. 0.34 ± 0.50; P = 0.030). Also, the HD group revealed significantly worse clinical outcomes. In conclusion, mid-term results of highly complex, severely calcified lesions requiring rotational atherectomy in non-HD patients were permissible as compared to on-label lesions. However, in HD patients, both angiographic and clinical outcomes were still suboptimal in this lesion subset, even using SES.

Coronary artery stent evaluation using a vascular model at 64-detector row CT: comparison between prospective and retrospective ECG-gated axial scans.

OBJECTIVE: We wanted to evaluate the performance of prospective electrocardiogram (ECG)-gated axial scans for assessing coronary stents as compared with retrospective ECG-gated helical scans. MATERIALS AND METHODS: As for a vascular model of the coronary artery, a tube of approximately 2.5-mm inner diameter was adopted and as for stents, three (Bx-Velocity, Express2, and Micro Driver) different kinds of stents were inserted into the tube. Both patent and stenotic models of coronary artery were made by instillating different attenuation (396 vs. 79 Hounsfield unit [HU]) of contrast medium within the tube in tube model. The models were scanned with two types of scan methods with a simulated ECG of 60 beats per minute and using display field of views (FOVs) of 9 and 18 cm. We evaluated the in-stent stenosis visually, and we measured the attenuation values and the diameter of the patent stent lumen. RESULTS: The visualization of the stent lumen of the vascular models was improved with using the prospective ECG-gated axial scans and a 9-cm FOV. The inner diameters of the vascular models were underestimated with mean measurement errors of -1.10 to -1.36 mm. The measurement errors were smaller with using the prospective ECG-gated axial scans (Bx-Velocity and Express2, p < 0.0001; Micro Driver, p = 0.0004) and a 9-cm FOV (all stents: p < 0.0001), as compared with the other conditions, respectively. The luminal attenuation value was overestimated in each condition. For the luminal attenuation measurement, the use of prospective ECG-gated axial scans provided less measurement error compared with the retrospective ECG-gated helical scans (all stents: p < 0.0001), and the use of a 9-cm FOV tended to decrease the measurement error. CONCLUSION: The visualization of coronary stents is improved by the use of prospective ECG-gated axial scans and using a small FOV with reduced blooming artifacts and increased spatial resolution.

Assessment of coronary stent in vitro on multislice computed tomography angiography: improved in-stent visibility by the use of 140-kV tube voltage.

OBJECTIVE: To assess the effect of tube voltage on the in-stent visibility of coronary stents in vitro on computed tomography (CT) angiography. METHODS: A total of 6 vascular models (3 models without stenosis and 3 with stenosis) using 3 kinds of stent (Bx Velocity, Express2, and Driver) with an inner diameter of approximately 3.5 mm and filled with contrast material (CT attenuation, 450 Hounsfield units) were scanned by means of a 16-detector row CT. We assessed the visual stenosis evaluation and inhomogeneity of stent lumen in 4 orientations (0-, 30-, 60-, and 90-degree angles) relative to the z-axis of the scanner using 3 imaging techniques (120-kV tube voltage using a medium convolution kernel, 120-kV tube voltage using a convolution kernel for bone, and 140-kV tube voltage using a convolution kernel for bone). Statistical analysis involved F test with a statistical significance of P < 0.05. RESULTS: The convolution kernel for bone made it easier to evaluate the stenosis inside the stents, although it increased the luminal inhomogeneity significantly (Bx Velocity and Express2, P < 0.005; Driver, P < 0.05). The luminal inhomogeneity tended to increase as the strut diameter and the weight per unit length increased. Using 120-kV tube voltage, the luminal inhomogeneity inside the stents was at the minimum in the angle of 0 degree relative to the z-axis, and at the maximum in the angle of 90 degrees, except for Driver. The 140-kV tube voltage was effective for the improvement of luminal inhomogeneity and visibility of in-stent stenosis compared with the 120-kV tube voltage. CONCLUSIONS: The in-stent visibility of coronary stents on CT angiography can be improved by the use of 140-kV tube voltage with the convolution kernel for bone.

Accuracy of attenuation measurement of vascular wall in vitro on computed tomography angiography: Effect of wall thickness, density of contrast medium, and measurement point.

OBJECTIVES: We sought to assess the effects of measurement point, wall thickness, and intravascular density of contrast material on attenuation measurement of vascular wall. MATERIALS AND METHODS: We used vascular models (actual attenuation value of the wall: 83 HU) with wall thicknesses of 1.5, 1.0, or 0.5 mm, filled with contrast material of 254, 325, or 400 HU. The 9 vascular models were fixed in an oil-filled container and scanned with a 16-detector computed tomography. The wall attenuation values were measured at 1 point for 0.5-mm thickness models, 3 for 1.0-mm thickness models, and 5 for 1.5-mm thickness models with the same interval of 0.25 mm. Total 20 measurements were done for each point. RESULTS: For 1.0-mm and 1.5-mm thickness models, wall attenuation progressively increased as the measurement points approached the lumen (P < 0.0001). At all the measurement points for 0.5-mm and 1.0-mm thickness models and the 2 inner measurement points for 1.5-mm thickness models, the densities of contrast material affected the wall attenuations significantly (P < 0.0001). At the midportion for 1.5-mm thickness models, the wall attenuations were not affected by the densities of the contrast material (P = 0.6301), and were 65-68 HU. CONCLUSIONS: The effects of the intravascular density of contrast material, measurement point, and wall thickness should be considered in the attenuation measurement of the wall.

Impact of 16-slice computed tomography in percutaneous coronary intervention of chronic total occlusions.

The main reason for failure of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) is because the calcified plaque prevents the guide wire crossing the occlusion. We aimed to identify the route, and characterize plaque components within CTO, using 16-slice computed tomography (MSCT). Twenty three angiographic CTO in 22 patients (mean age 69 +/- 5 years, 17 males) were included. All patients had undergone MSCT prior to PCI. Images were analyzed for lesion visibility and plaque characteristics of CTO. The presence and location of calcified plaque within the CTO were systematically assessed. Each lesion was classified as a noncalcified, moderately calcified, or exclusively calcified plaque. Procedural failure was defined as the inability to cross a guide wire through the occlusion. All coronary routes of CTO segment were visualized. MSCT revealed three markedly bent CTO segments (13.0%), which could not be identified by coronary angiography only. Calcified plaques were detected in 30 lesions of 19 CTO segments (82.6%), but were not detected in the other four. The majority of calcified plaque was located in the proximal lesion, or both proximal and distal lesions. Fifteen out of 30 calcified lesions (50.0%) were exclusively calcified plaques. Overall procedural success was obtained in 21 CTOs (91.3%). MSCT can accurately identify the route of the CTO segment and evaluate both distribution and amount of the calcified plaque within it. Even with the complicated and/or calcified lesions, PCI success rate was excellent under MSCT guidance. MSCT should become a useful tool in PCI of CTO.

Accuracy and efficiency of left ventricular ejection fraction analysis, using multidetector row computed tomography: effect of image reconstruction window within cardiac phase, slice thickness, and interval of short-axis sections.

BACKGROUND: The aim of the present study was to assess the accuracy and efficiency of left ventricular ejection fraction (LVEF) analysis by multidetector row computed tomography (CT). METHODS AND RESULTS: The CT data of 21 patients were analyzed by semi-automated software on a workstation. In analysis of LVEF using systolic volumes in the 6 phases (30-55%), systolic images of 10% interval (35, 45, 55%) were underestimated with a mean measurement error of -0.4% and the standard error of the estimate (SEE) of 0.6%, compared with the LVEF using images of 5% interval. In analysis of LVEF using 3-slice thicknesses of axial images (1, 2, and 3 mm), and 3-slice numbers of short-axis sections (10 14, and 30 slices), there was no significant difference between the SEE of the intraobserver reproducibility and that of the analysis with 30 short-axis sections using axial images of 1-, 2- and 3-mm thickness, and that with 14 short-axis sections using axial images of 1- and 2-mm thickness. The mean analysis times were 96.9 s, 119.8 s, and 227.0 s for the analysis with 10, 14, and 30 short-axis sections, respectively. CONCLUSION: The proper selection of the reconstruction interval in the cardiac phase, the slice thickness of the axial images, and the number of short-axis sections reduces the analysis time, maintaining the accuracy of LVEF analysis. This will be acceptable for practical use at present, although more accurate analysis is preferable.

Laser-induced liquid-to-droplet extraction of chlorophenol: photothermal phase separation of aqueous triethylamine solutions.

Thermal phase separation of aqueous triethylamine (TEA) solutions (TEA wt % = 6.5-6.7 in H2O) was induced by irradiating a focused 1064-nm laser beam (spot size approximately 1 mum) under an optical microscope, and this produced a single micrometer-sized TEA droplet as demonstrated by in situ Raman microspectroscopy. Since H2O absorbs 1064-nm light, heat is generated at the focal spot of the incident laser beam, giving rise to photothermal phase separation of the aqueous TEA solution. The TEA droplet produced by phase separation was trapped simultaneously by the incident laser beam. In the presence of p-chlorophenol (CP) in an aqueous TEA solution, laser-induced photothermal phase separation and simultaneous TEA droplet formation brought about extraction/concentration of CP from the surrounding solution phase to the TEA droplet (approximately 15-mum diameter and 1.7-pL volume). Raman microspectroscopy demonstrated that the distribution coefficient of CP (KD) between the solution phase and the single TEA droplet was KD(drop) = approximately 21, while that in a bulk TEA/H2O system was KD(bulk) = 4.7. The larger KD(drop) value as compared to KD(bulk) was discussed in terms of radiation pressure exerted on CP in the TEA droplet.