Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation.

Background We evaluated the importance of high-density lipoprotein (HDL) functionality for target-lesion revascularization in patients treated with coronary stents using a rapid cell-free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol-uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow-up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow-up was performed to assess target-lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P<0.001). The CUC showed a significant inverse correlation with incidence of target-lesion revascularization (odds ratio, 0.887; P=0.003) and with lipid accumulation inside stents, suggesting that neoatherosclerosis contributes to the association between CUC and target-lesion revascularization. Conclusions Impaired HDL functionality, detected as decreased CUC, might lead to future stent failure by provoking atherogenic changes of the neointima within stents. Both quantitative and qualitative assessments of HDL might enable the improved prediction of clinical outcomes after stent implantation.

Impact of Cytochrome P450 2C19 Reduced-Function Polymorphism on Lesions and Clinical Outcome in Japanese Patients After Drug-eluting Stent Implantation.

We previously reported that the cytochrome P450 (CYP) 2C19 reduced-function polymorphism was associated with decreased responsiveness to clopidogrel and intra-stent thrombus formation, as well as subsequent ischemic events after drug-eluting stent (DES) implantation. However, the relationship between the polymorphism and bleeding events remains unclear. Among 1427 consecutive patients who underwent DES implantation at Kobe University Hospital, 247 patients (341 lesions) were enrolled for this prospective observational study. All patients underwent follow-up optical coherence tomography (OCT) at 8 months and CYP2C19 genotyping. The patients were divided into three groups according to the phenotypic effect of the CYP2C19 polymorphism: extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). OCT findings, and ischemic and bleeding events were compared among the three groups. The frequency of intra-stent thrombi showed an increasing pattern among the patients with EM, IM, and PM (13.3%, 22.6%, and 33.3%, respectively; p = 0.04). The incidence of major adverse cardiovascular events (MACE) also showed an increase across the three groups from extensive to poor metabolizers (7.8%, 10.5%, and 33.3%, respectively; p < 0.01), whereas the frequency of bleeding showed no significant difference among the groups (15.6%, 19.4%, and 21.2%, respectively; p = 0.69). The CYP2C19 polymorphism is associated with the frequency of MACE, but is not related to the incidence of bleeding after percutaneous coronary intervention in Japanese patients receiving clopidogrel.

Data on impact of monocytes and glucose fluctuation on plaque vulnerability in patients with coronary artery disease.

Data presented in this article are supplementary material to our research article entitled "Impact of CD14++CD16+ monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients" [1]. This article contains the data of study population, diagnostic ability of CD14++CD16+ monocytes to identify thin-cap fibroatheromas, and association between laboratory variables and plaque properties.

Relationship between the membranous septum and the virtual basal ring of the aortic root in candidates for transcatheter implantation of the aortic valve.

Knowledge of the anatomy of the membranous septum, as a surrogate to the location of the atrioventricular conduction axis, is a prerequisite for those undertaking transcatheter implantation of the aortic valve (TAVI). Equally important is its relationship of the virtual basal ring. This feature, however, has yet to be adequately described in the living heart. We analyzed computed tomographic angiographic datasets from 107 candidates (84.1 ± 5.2 years, 68% women) for TAVI. Using multiplanar reconstructions, we measured the height and width of the membranous septum, and the distances of its superior and inferior margins from the virtual basal ring plane. We also assessed the extent of wedging of the aortic root between the mitral valve and the ventricular septum. Mean heights and widths of the membranous septum were 6.6 ± 2.0, and 10.2 ± 3.1 mm, respectively, with its size significantly associated with that of the aortic root (P < 0.05). Its superior and inferior margins were 4.5 ± 2.3 and 2.1 ± 2.1 mm, respectively, from the plane of the basal ring. The inferior distance, the surrogate for the adjacency of the atrioventricular conduction axis, was ≤ 5mm in 91% of the patients. Deeper wedging of the aortic root was independently correlated with a shorter inferior distance (ß = 0.0569, P = 0.0258). The membranous septum is appreciably closer to the virtual basal ring than previously appreciated. These findings impact on estimations of the risk of damage to the atrioventricular conduction axis during TAVI. Clin. Anat. 31:525-534, 2018. © 2018 Wiley Periodicals, Inc.

Impact of CD14++CD16+ monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients.

BACKGROUND AND AIMS: This study examined the impact of CD14++CD16+ monocytes on coronary plaque vulnerability, as assessed by optical coherence tomography (OCT), and investigated their association with daily glucose fluctuation. Although increased CD14++CD16+ monocyte levels have been reported to increase cardiovascular events, their impact on coronary plaque vulnerability in coronary artery disease (CAD) patients with or without diabetes mellitus (DM) remains unclear. METHODS: This prospective observational study included 50 consecutive patients with CAD, receiving lipid-lowering therapy and undergoing coronary angiography and OCT. Patients were divided into 3 tertiles according to the CD14++CD16+ monocyte percentages assessed by flow cytometry. Standard OCT parameters were assessed for 97 angiographically intermediate lesions (diameter stenosis: 30-70%). Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). RESULTS: CD14++CD16+ monocytes negatively correlated with fibrous cap thickness (r = -0.508, p < 0.01). The presence of thin-cap fibroatheroma (TCFA) was increased stepwise according to the tertile of CD14++CD16+ monocytes (0 [tertile 1] vs. 5 [tertile 2] vs. 10 [tertile 3], p < 0.01). CD14++CD16+ monocytes were a significant determinant of TCFA (OR 1.279, p = 0.001). In non-DM patients, a significant relationship was found between CD14++CD16+ monocytes and MAGE (r = 0.477, p = 0.018). CONCLUSIONS: CD14++CD16+ monocytes were associated with coronary plaque vulnerability in CAD patients with well-regulated lipid levels both in DM and non-DM patients. Cross-talk between glucose fluctuation and CD14++CD16+ monocytes may enhance plaque vulnerability, particularly in non-DM patients. CD14++CD16+ monocytes could be a possible therapeutic target for coronary plaque stabilization.

The impact of serum trans fatty acids concentration on plaque vulnerability in patients with coronary artery disease: Assessment via optical coherence tomography.

BACKGROUND AND AIMS: Recent epidemiological studies have showed that excessive intake of trans fatty acids (TFA) can be a residual risk for the development of coronary artery disease (CAD) even under medical management, including statins. This study aimed at investigating the association between lipid profile, including serum TFA concentration, and plaque vulnerability using optical coherence tomography (OCT). METHODS: The level of serum elaidic acid, a major TFA component, was measured using gas chromatography in 161 consecutively enrolled patients with CAD under guideline-directed risk factor management. OCT was performed to evaluate morphological features of angiographic intermediate stenosis (30% < diameter of stenosis <70%). OCT data were also used to measure lipid index (LI), defined as mean lipid arc multiplied by lipid length, and determine the presence of thin-cap fibroatheroma (TCFA), defined as a lipid-rich plaque with the smallest fibrous cap thickness <65 µm and the maximal arc >90°. RESULTS: Among 190 lesions assessed using OCT, 49 TCFAs were detected. In patients with at least one TCFA lesion, levels of elaidic acid (12.9 ± 4.9 vs. 10.3 ± 4.3 µmol/L, p = 0.001), triglycerides (169 ± 81 vs. 130 ± 60 mg/dL, p = 0.005), and remnant-like particle cholesterol (10.4 ± 6.5 vs. 7.7 ± 4.7 mg/dL, p = 0.005) were higher than in those without TCFAs. Generalized estimating equations identified elaidic acid level as the independent risk factor of TCFA. LI had a positive correlation with elaidic acid level (r = 0.173, p = 0.025). CONCLUSIONS: TFA may affect plaque vulnerability in patients with CAD. Serum TFA concentration may represent another cardiovascular risk factor during conventional risk factor management.

Diversity and Determinants of the Three-dimensional Anatomical Axis of the Heart as Revealed Using Multidetector-row Computed Tomography.

The location of the heart within the thorax varies significantly between individuals. The resultant diversity of the anatomical cardiac long axis, however, and its determinants, have yet to be systematically investigated. We enrolled 100 consecutive patients undergoing coronary arterial computed tomographic angiography, decomposing the vector of the anatomical cardiac long axis by projecting it to horizontal, frontal, and sagittal planes. The projected vectors on each plane were then converted into three rotation angles using coordinate transformation. We then measured the extent of aortic wedging, using the vertical distance between the inferior margins of the non-adjacent aortic sinus and the epicardium. We took the aortic root rotation angle to be zero when an "en face" view of the right coronary aortic sinus was obtained in the frontal view, defining leftward rotation to be positive. The mean horizontal, frontal, and sagittal rotation angles were 48.7° ± 9.5°, 52.3° ± 12.0°, and 34.0° ± 11.2°, respectively. The mean extent of aortic wedging, and the aortic root rotation angle, were 42.7 ± 9.8 mm, and 5.3° ± 16.4°. Horizontal rotation of the anatomical axis was associated with leftward and ventral rotation, and vice versa. Multivariate analysis showed aortic root rotation to be associated with horizontal cardiac rotation, while aortic wedging is associated with frontal and sagittal cardiac rotation. We have quantified the marked individual variation observed in the anatomical axis of the living heart, identifying the different mechanisms involved in producing the marked three-dimensional diversity of the living heart. Anat Rec, 300:1083-1092, 2017. © 2017 Wiley Periodicals, Inc.

The differences between bisecting and off-center cuts of the aortic root: The three-dimensional anatomy of the aortic root reconstructed from the living heart.

BACKGROUND: It is axiomatic that the diameter of the virtual basal ring of the aortic root, which is elliptical rather than circular, will differ when assessed using between bisecting as opposed to off-center cuts. Such differences, however, which pertain directly to echocardiographic assessments of the so-called valvar annulus, have yet to be systematically explored. METHODS: We retrospectively analyzed 30 patients undergoing coronary computed tomographic angiography, measuring the virtual basal ring diameter using routine multiplanar reconstructions. We made orthogonal bisecting cuts from the nadir of the hinge of the right coronary aortic leaflet to the center of the opposite inter-leaflet fibrous triangle between the noncoronary and left coronary aortic leaflets. We compared these measurements with orthogonal off-center cuts made through the nadirs of the hinges of the adjacent leaflets. RESULTS: The measured diameter of the virtual basal ring was significantly longer when measured using the bisecting cut as opposed to all off-center cuts (mean difference: 1.35±1.34 mm, P<.0001; 0.77±0.95 mm, P=.0001, respectively). The measured diameters of the sinuses of Valsalva, in contrast, were significantly shorter when measured using the bisecting cut (mean difference: -3.24±1.38 mm, P<.0001; -2.86±1.61 mm, P<.0001). CONCLUSIONS: There are significant differences in the diameters of the aortic root, which represent the echocardiographic annulus, when measured using bisecting as opposed to off-center cuts. Account should be taken of these differences when using cross-sectional echocardiographic measurements to assess the dimensions of the aortic root.

Effects of daily glucose fluctuations on the healing response to everolimus-eluting stent implantation as assessed using continuous glucose monitoring and optical coherence tomography.

BACKGROUND: Several studies have revealed that glucose fluctuations provoke oxidative stress that leads to endothelial cell dysfunction, progression of coronary atherosclerosis, and plaque vulnerability. However, little is known regarding their effect on neointimal growth after stenting in patients with coronary artery disease (CAD). We aimed to investigate the effects of glucose fluctuations on neointimal growth after everolimus-eluting stent (EES) implantation. METHODS: This study examined 50 patients who underwent a 9-month follow-up using optical coherence tomography (OCT) after EES implantation. Glucose fluctuation was expressed as the mean amplitude of glycemic excursion (MAGE), and was determined via continuous glucose monitoring before stenting. At the OCT follow-up, we evaluated the percentage of uncovered struts and three-dimensional uniformity of neointimal distribution by calculating the mean neointimal thickness (NIT) within 360 equally-spaced radial sectors for every 1-mm cross-sectional OCT analysis, and assessed the incidence of major adverse cardiovascular events (MACE). RESULTS: We evaluated 60 lesions in 50 patients. Linear mixed effect models were used to explore the influence of different variables on variability in NIT and the percentage of uncovered struts and to adjust for covariates. Univariate analysis showed that MAGE was most strongly correlated with the previously mentioned OCT measurements (coefficient ß ± standard error = 0.267 ± 0.073 and 0.016 ± 0.003, t = 3.668 and 6.092, both P < 0.001, respectively). In multivariate analysis, MAGE had the strongest effect on variability in NIT (coefficient ß ± standard error = 0.239 ± 0.093, P = 0.014) and the percentage of uncovered struts (coefficient ß ± standard error = 0.019 ± 0.004, P < 0.001). Five lesions in four patients required target lesion revascularization (10.0 %) at a mean duration of 9 months after EES implantation. Compared to non-MACE cases, cases of MACE exhibited a significantly higher MAGE (99 vs. 68; P = 0.004), maximum NIT (580 vs. 330 µm; P = 0.002), and variability in NIT (100 vs. 65; P = 0.007), although there was no significant difference in these groups' HbA1c levels. CONCLUSIONS: Glucose fluctuation may affect vessel healing after EES implantation in patients with CAD who are receiving lipid-lowering therapy. Therefore, glucose fluctuations may be an important target for secondary prevention after coronary stenting, which is independent of dyslipidemia control.