Aims: The anti-inflammatory effects of the xanthine oxidase inhibitor, febuxostat, a urate-lowering agent, have been reported in animal studies. However, the anti-inflammatory effects of ...urate-lowering therapy and its associated cardiovascular protective effects have not been fully determined in actual clinical practice. This study aimed to investigate the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and to assess for potential correlations between changes in WBC count and inflammatory biomarkers and atherosclerosis in this patient population.Methods: This was a post hoc subanalysis of the PRIZE study, a multicenter, prospective, randomized, open-label clinical trial. In the PRIZE study, asymptomatic hyperuricemia patients were randomized to febuxostat group or control group with non-pharmacological therapy and evaluated the effect on vascular. The primary endpoints of this study were the assessment of the time course of WBC count over 24 months and its changes from baseline. Correlations of WBC count with high-sensitivity C-reactive protein (hs-CRP) and mean common carotid artery (CCA)-IMT were also exploratorily examined in the febuxostat group.Results: A total of 444 patients (febuxostat group, n=223; control group, n=221) with WBC measurements available at baseline and at least one of the follow-up time points of 12 or 24 months, were enrolled. Febuxostat modestly, but significantly, reduced WBC counts at 12 and 24 months compared with the baseline levels (P=0.002 and P=0.026, respectively). Notably, the WBC count in the febuxostat group at 12 and 24 months was significantly lower than that in the control group (P=0.007 and P=0.023, respectively). The changes in WBC count were associated with those of hs-CRP (P=0.038), but not with CCA-IMT (P=0.727).Conclusions: Febuxostat therapy for 24 months modestly, but significantly, decreased WBC count in patients with asymptomatic hyperuricemia. This might potentially reflect a modest anti-inflammatory action of febuxostat in clinical settings.
Although the simple single stenting rather than complex double stenting is recommended on percutaneous coronary intervention (PCI) for bifurcation lesions, double stenting cannot always be avoided. ...We investigated the impact of directional coronary atherectomy (DCA), followed by drug-coated balloon (DCB) treatment to reduce the number of stents and avoid complex stenting in PCI for bifurcation lesions and short-term patency. DCA treatment without stents was attempted for 27 bifurcation lesions in 25 patients, of those, 26 bifurcation lesions in 24 patients were successfully treated and 3-month follow-up angiography and optical coherence tomography (OCT) were performed. Sixteen lesions (59.3%) were related to left main trunk distal bifurcations, and 7 (25.9%) were true bifurcation lesions. Among the true bifurcation lesions, 4 lesions (57.1%) needed 1 stent, and the other 3 lesions (42.9%) needed no stents. Among the non-true bifurcation lesions, 1 lesion (5.0%) needed bailout stent and other lesions (95.0%) needed no stents. According to DCA followed by DCB treatment, the angiographic mean diameter stenosis improved from 65.5 ± 15.0% to 7.8 ± 9.8%, and the mean plaque area in intravascular ultrasound improved from 80.4 ± 10.5% to 39.0 ± 11.5%, respectively. Angiographic and OCT late lumen loss values were 0.2 ± 0.6 mm and 1.4 ± 1.9 mm, respectively. No patient had in-hospital major adverse cardiac events (MACE) and 3-month MACE. In conclusion,
c
ompared with standard provisional side branch stenting strategy, DCA followed by DCB treatment might reduce the number of stents, avoid complex stenting for major bifurcation lesions and provide good short-term outcomes.
Background:Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of ...platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.Methods and Results:We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events.Conclusions:Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).
Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial ...infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI).
In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06).
Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI.
CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.
Background The relationship between gut microbiota and in vivo coronary plaque characteristics has not been reported. This study was conducted to investigate the relationship between gut microbiota ...and coronary plaque characteristics in patients with coronary artery disease. Methods and Results Patients who underwent both optical coherence tomography and intravascular ultrasound imaging and provided stool and blood specimens were included. The composition of gut microbiota was evaluated using 16S rRNA sequencing. A total of 55 patients were included. At the genus level, 2 bacteria were associated with the presence of thin‐cap fibroatheroma, and 9 bacteria were associated with smaller fibrous cap thickness. Among them, some bacteria had significant associations with inflammatory/prothrombotic biomarkers. Dysgonomonas had a positive correlation with interleukin‐6, Paraprevotella had a positive correlation with fibrinogen and negative correlation with high‐density lipoprotein cholesterol, Succinatimonas had positive correlations with fibrinogen and homocysteine, and Bacillus had positive correlations with fibrinogen and high‐sensitivity C‐reactive protein. In addition, Paraprevotella , Succinatimonas , and Bacillus were also associated with greater plaque volume. Ten bacteria were associated with larger fibrous cap thickness. Some were associated with protective biomarker changes; Anaerostipes had negative correlations with trimethylamine N‐oxide, tumor necrosis factor α, and interleukin‐6, and Dielma had negative correlations with trimethylamine N‐oxide, white blood cells, plasminogen activator inhibitor‐1, and homocysteine, and a positive correlation with high‐density lipoprotein cholesterol. Conclusions Bacteria that were associated with vulnerable coronary plaque phenotype and greater plaque burden were identified. These bacteria were also associated with elevated inflammatory or prothrombotic biomarkers. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000041692.
Percutaneous coronary intervention (PCI) for complex lesions is still technically demanding and is associated with less favorable procedural parameters such as lower success rate, longer procedural ...time, higher contrast volume and unexpected complications. Because the conventional angiographic analysis is limited by the inability to visualize the plaque information and the occluded segment, cardiac computed tomography has evolved as an adjunct to invasive angiography to better characterize coronary lesions to improve success rates of PCI. Adding to routine image reconstructions by coronary computed tomography angiography, the thin-slab maximum intensity projection method, which is a handy reconstruction technique on an ordinary workstation, could provide easy-to-understand images to reveal the anatomical characteristics and the lumen and plaque information simultaneously, and then assist to build an in-depth strategy for PCI. Especially in the treatment of chronic total occlusion lesion, these informations have big advantages in the visualization of the morphologies of entry and exit, the occluded segment and the distribution of calcium compared to invasive coronary angiography. Despite of the additional radiation exposure, contrast use and cost for cardiac computed tomography, the precise analysis of lesion characteristics would consequently improve the procedural success and prevent the complication in complex PCI.
Optical coherence tomography (OCT) is recommended to be the most appropriate modality in assessing calcium thickness, however, it has limitations associated with infrared attenuation. Although ...coronary computed tomography angiography (CCTA) detects calcification, it has low resolution and hence not recommended to measure the calcium size. The aim of this study was to devise a simple algorithm to estimate calcium thickness based on the CCTA image. A total of 68 patients who had CCTA for suspected coronary artery disease and subsequently went on to have OCT were included in the study. 238 lesions of them divided into derivation and validation dataset at 2:1 ratio (47 patients with 159 lesions and 21 with 79, respectively) were analyzed. A new method was developed to estimate calcium thickness from the maximum CT density within the calcification and compared with calcium thickness measured by OCT. Maximum Calcium density and measured calcium-border CT density had a good correlation with a linear equation of
y
= 0.58
x
+ 201 (
r
= 0.892, 95% CI 0.855–0.919,
p
< 0.001). The estimated calcium thickness derived from this equation showed strong agreement with measured calcium thickness in validation and derivation dataset (
r
2
= 0.481 and 0.527, 95% CI 0.609–0.842 and 0.497–0.782,
p
< 0.001 in both, respectively), more accurate than the estimation by full width at half maximum and inflection point method. In conclusion, this novel method provided the estimation of calcium thickness more accurately than conventional methods.
This study aims to elucidate 1-year clinical outcomes using this technique for patients with stage 4 or 5 advanced chronic kidney disease (CKD). Research has proven that imaging-guided percutaneous ...coronary intervention (PCI) reduces contrast volume significantly; however, only short-term clinical benefits have been reported. Minimum-contrast (MINICON) studies are based on the registry design pattern to enroll PCI results in patients with advanced CKD stage 4 or 5 comorbid with coronary artery disease. We excluded cases of emergency PCI or maintenance dialysis from this study. In this study, we compared the intravascular ultrasound (IVUS)-guided MINICON PCI group (
n
= 98) with the angiography-guided standard PCI group (
n
= 86). Enrollment of the MINICON studies started in 2006. Before 2012, IVUS-guided MINICON PCI was performed only in 14% (stage 1), but it was 100% after 2012 (stage 2). The enrollment finished in 2016. The IVUS-guided MINICON PCI group exhibited a significantly reduced contrast volume (22 ± 20 vs. 130 ± 105 mL;
P
< 0.0001) and contrast-induced acute kidney injury (CI-AKI; 2% vs. 15%;
P
= 0.001). The PCI success rate was similarly high (100% vs. 99%;
P
= 0.35). At 1 year (follow-up rate, 100%), we observed less induction of renal replacement therapy (RRT; 2.7% vs. 13.6%;
P
= 0.01), but all-cause mortality or myocardial infarction was similar in both groups. The IVUS-guided MINICON PCI reduces CI-AKI significantly and induction of RRT at 1 year in patients with stage 4 or 5 advanced CKD.
Objectives. To investigate the relationship between the eccentric calcification of aortic valve and transcatheter heart valve (THV) distortion and the impact of THV distortion on echo parameters and ...clinical outcomes. Background. The effects of eccentric calcification of the aortic valve on the THV distortion and the relationship between THV distortion and clinical impact were not fully understood. Methods. Patients with symptomatic severe aortic stenosis who were undergoing THV implantation were enrolled. Patients underwent preprocedural, postprocedural multislice computed tomography (MSCT), and follow-up transthoracic echocardiogram (TTE). Delta calcium score (ΔCS) is defined as the difference between the maximum and minimal calcium scores of the three cusps, while valve distortion score (VDS) is defined as the difference between the longest and shortest stent frame, as obtained using MSCT. Patients were divided into two groups according to ΔCS: “noneccentric calcification group” and “eccentric calcification group.” Results. A total of 118 patients were enrolled (59 patients in noneccentric and 59 in eccentric calcification groups). VDS was significantly lower in the noneccentric calcification group than in the eccentric calcification group (1.31 ± 0.82 mm vs. 1.73 ± 0.76 mm, p=0.004). VDS was not associated with the degree of paravalvular leak (PVL) and aortic valvular mean pressure gradient (AVPG) at 30-day and 1-year follow-up TTE and the cumulative rates of all-cause death and rehospitalization at 2-year clinical follow-up. Conclusions. Eccentric valvular calcification was associated with longitudinal THV distortion. However, THV distortion was not associated with PVL, AVPG, and adverse clinical events during midterm follow-up.
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