Hachidai Takahashi

Effect of Daily Glucose Fluctuation on Coronary Plaque Vulnerability in Patients Pre-Treated With Lipid-Lowering Therapy: A Prospective Observational Study

OBJECTIVES This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy. BACKGROUND There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD. METHODS This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit lesions were assessed by virtual histology intravascular ultrasound, and the volume percentage of necrotic core within the plaque (%NC) and the presence of thin-cap fibroatheroma were evaluated. RESULTS In total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p <0.001). A linear mixed effect model showed that MAGE had the strongest effect on %NC (coefficient β = 0.080 ± 0.020 [standard error], p < 0.001). The generalized linear mixed effect model revealed that MAGE was the only independent predictor of the presence of thin-cap fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p = 0.007). CONCLUSIONS Daily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients.

Serial Optical Coherence Tomography Evaluation at 6, 12, and 24 Months After Biolimus A9-Eluting Biodegradable Polymer-Coated Stent Implantation

BACKGROUND The Nobori (Terumo Corporation, Tokyo, Japan) is a biolimus A9-eluting stent (BES) featured with a biodegradable polymer coated on the abluminal side only. We previously reported that favourable vessel healing was achieved at 6-12 months after BES implantation. However, detailed long-term vessel reaction after BES deployment is unclear. METHODS Twenty-two BESs were serially evaluated using optical coherence tomography (OCT) at 6, 12, and 24 months after stenting. Average neointimal thickness, uncovered struts, and neointimal unevenness score (each cross-section as maximum neointimal thickness in 1 cross section divided by the average neointimal thickness of the same cross-section) were manually measured. In addition, we evaluated the percentage of struts with peri-strut low-intensity area (a region around stent struts that homogenously showed less intensity than the surrounding tissue, which suggests fibrin deposition or impaired neointima maturation), thrombi, and atherogenic neointimas (neointimas containing a diffuse border and poor-signal region with invisible struts due to marked signal attenuation). RESULTS Serial OCT observation revealed a small gradual increase in neointimal thickness from 6 to 24 months (73 ± 24 μm; 81 ± 26 μm; and 108 ± 35 μm, respectively, P = 0.001) with a nonsignificant decrease in the lumen area (6.36 ± 1.98 mm(2); 6.18 ± 2.04 mm(2); and 5.87 ± 2.06 mm(2); P = 0.72). Frequency of uncovered struts (3.89 ± 3.91%; 1.55 ± 1.63%; and 0.23 ± 0.67%; P = 0.001), neointimal unevenness score (1.95 ± 0.18% to 1.86 ± 0.19% to 1.78 ± 0.17; P = 0.012), percentage of thrombi (5%, 0%, and 0%; P = 0.37) and peri-strut low-intensity area (6.8%, 5.1%, and 1.6%; P = 0.017) decreased from 6 to 12 and 24 months. Atherogenic neointima was not observed in the event-free OCT cohort. CONCLUSIONS The Nobori stent achieved acceptable long-term vessel healing, mostly without adverse vessel reactions.

Impact of cytochrome P450 2C19 loss-of-function polymorphism on intra-stent thrombi and lesion outcome after everolimus-eluting stent implantation compared to that after first-generation drug-eluting stent implantation

BACKGROUND The contribution of clopidogrel response due to cytochrome P450 (CYP) 2C19 loss-of-function polymorphism after drug-eluting stent (DES) implantation is unclear. METHODS A total of 196 patients who had undergone optical coherence tomography (OCT) at 8 months following first-generation DES (120 lesions) and current-generation everolimus-eluting stent (EES) implantation (127 lesions) were enrolled. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs). OCT findings were compared among the 3 groups. Responsiveness to clopidogrel was assessed by VerifyNow platelet reactivity unit (PRU). RESULTS The incidence of intra-stent thrombi was significantly higher after first-generation DES implantation compared with EES implantation (35% vs 13%, respectively; p=0.0001). In the first-generation DES group, the incidence of intra-stent thrombi significantly increased among EMs, IMs, and PMs (21% vs 36% vs 63%, respectively; p=0.007), while there was no significant difference among the 3 groups after EES implantation (10% vs 13% vs 20%, respectively; p=0.55). The PRU significantly increased among EMs, IMs, and PMs in each stent group. In multivariate analyses, although PMs had a 3-fold higher risk of thrombi formation compared with non-PMs after first-generation DES implantation, there were no significant differences in thrombi formation between the 2 groups after EES implantation. The optimal PRU cutoff values for the prediction of intra-stent thrombi with first-generation DES and EES were 234 and 256, respectively. CONCLUSION CYP2C19 loss-of-function polymorphism is associated with a higher incidence of intra-stent thrombi after first-generation DES implantation, while the impact is attenuated following EES implantation.

Impact of CD14 ++ CD16 + monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients with well-regulated lipid levels

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.

Impact of final kissing balloon inflation on vessel healing following drug-eluting stent implantation: Insight from the optical coherence tomography sub-study of the J-REVERSE trial

BACKGROUND We sought to clarify the impact of final kissing inflation (FKI) after single stenting of bifurcation lesions on vessel healing. METHODS From the J-REVERSE registry enrolling 303 bifurcation lesions treated with provisional single stenting using sirolimus- (SES) or everolimus-eluting stent (EES), 65 lesions treated with (n=30) and without (n=35) FKI underwent 9-month follow-up optical coherence tomography. Average stent eccentricity index (SEI: minimum/maximum stent diameter) and neointimal unevenness score (NUS: maximum/average neointimal thickness of the same cross-section) for the proximal, bifurcation, and distal segments were compared between FKI and non-FKI groups. RESULTS At the proximal segment, the FKI group demonstrated significantly larger average stent area with greater asymmetric stent expansion, and average lumen area remained significantly larger at 9-month follow-up despite a tendency toward greater neointimal proliferation. Jailed strut and thrombus incidence were also significantly lower at the side branch orifice, and NUS was significantly smaller at the bifurcation and proximal segments in the FKI group. CONCLUSIONS Nine months after SES and EES treatment of bifurcation lesions, FKI reduced proximal-segment luminal narrowing. Considering its homogeneous neointimal distribution and fewer jailed struts, FKI may be beneficial for treating bifurcation lesions.

Impact of residual platelet reactivity under clopidogrel treatment for lesions and the clinical outcome after drug-eluting stent implantation in patients with hemodialysis

BACKGROUND Hemodialysis (HD) patients are at high risk for adverse clinical outcomes after drug-eluting stent (DES) implantation. However, the impact of residual platelet reactivity under dual anti-platelet therapy in this subset of patients remains unclear. METHODS We enrolled 142 stable angina patients (194 lesions) treated with DES, who were taking aspirin and 75mg clopidogrel and had undergone 8-month angiography with optical coherence tomography (OCT). OCT findings and major adverse cardiac events (MACEs) at 1 year (cardiac death, acute coronary syndrome, target lesion and vessel revascularization, and stent thrombosis) were compared between 28 HD patients and 114 non-HD patients. Responsiveness to clopidogrel was assessed by measuring P2Y12 reaction unit (PRU) at 8 months. RESULTS PRU was significantly higher in HD patients than in non-HD patients (p=0.006), even though proportion of cytochrome P450 2C19 genotype was equivalent. HD patients had a significantly higher rate of thrombi formation (assessed using OCT) and MACEs than non-HD patients (thrombi: p=0.001; MACEs: p=0.0001). The PRU value was independently associated with MACEs in both groups. The optimal cutoff values of PRU for predicting MACEs were 235 for HD patients and 259 for non-HD patients. CONCLUSIONS HD was associated with a high residual platelet reactivity, which may contribute to the higher incidence of MACEs after DES implantation in HD patients. HD may be a patient profile that merits a more potent anti-platelet regimen.

Impact of Diabetes Mellitus on Intravascular Ultrasound-Guided Provisional Stenting in Coronary Bifurcation Lesions J-REVERSE Sub-Study

OBJECTIVE To investigate the impact of diabetes mellitus (DM) on provisional coronary bifurcation stenting under the complete guidance of intravascular-ultrasound (IVUS). BACKGROUND The efficacy of such intervention has not yet been fully elucidated in the DM patients. METHODS A total of 100 DM and 139 non-DM patients in a prospective multi-center registry of IVUS-guided bifurcation stenting were compared in angiographic results at 9 months. Vessel and luminal changes during the intervention were analyzed using the IVUS. Vascular healing at the follow-up was also investigated in 23 lesions in each group using optical coherence tomography (OCT). RESULTS No difference was detected regarding baseline reference vessel diameter and minimum lumen diameter in proximal main vessel (MV), distal MV, and side branch (SB). The rate of everolimus-eluting stent use (78.4% vs. 78.3%), final kissing inflation (60.1% vs. 49.0%), and conversion to 2-stent strategy (2.9% vs. 2.8%) were also similar. In the DM group, late loss was greater in proximal MV (DM 0.23 ± 0.29 vs. non-DM 0.16 ± 0.24 mm, P < 0.05) and SB (0.04 ± 0.49 vs. -0.08 ± 0.35 mm, P < 0.05). Smaller vessel area restricted stent expansion in the proximal MV (6.18 ± 1.67 vs. 6.72 ± 2.07 mm2 , P < 0.05). More inhomogeneous neointimal coverage (unevenness score, 1.90 ± 0.33 vs. 1.72 ± 0.29, P < 0.05) and more frequent thrombus attachment (26% vs. 4%, P < 0.05) were documented in the proximal MV at 9-month follow-up OCT. CONCLUSIONS Despite IVUS optimization for coronary bifurcation, DM is potentially associated with smaller luminal gain, higher late-loss, and inhomogeneous vascular healing with frequent thrombus attachment in the proximal MV.

Transient Ischemic Right Axis Deviation Tendency of the Frontal Plane QRS Axis in a Case of Inferior Myocardial Ischemia

A 73-year-old man was admitted to our hospital because of chest pain at rest. Electrocardiography (ECG) showed an ST-segment depression, a negative U-wave in the precordial leads, and a right axis deviation (RAD) tendency. Coronary angiography revealed occlusion of the right coronary artery. Collateral flow from the jeopardized left anterior descending artery to the posterior descending artery (PDA) was fair. After successful revascularization, improvement in the ECG findings was noted. Since blood supply to the left posterior fascicle is dependent on the PDA, the RAD tendency could be explained by the presence of a transient ischemic left posterior hemiblock.

Favorable early vessel healing after everolimus-eluting stent implantation: 3-, 6-, and 12-month follow-up of optical coherence tomography

BACKGROUND Although a prospective randomized control study revealed that 3-month dual anti-platelet therapy (DAPT) is safe and does not compromise the efficacy of everolimus-eluting stent (EES) in selected patients, detailed vessel healing at early phase after EES implantation has yet to be investigated in Japanese patients. METHODS AND RESULTS A total of 27 lesions in 19 patients treated with EES were serially evaluated by using optical coherence tomography (OCT) at 3, 6, and 12 months after stent implantation. In addition to standard quantitative OCT parameters, the percentage of stents with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (63±17μm; 83±30μm; and 111±44μm, respectively; p=0.006) and small decrease in average lumen area (6.80±2.57mm2, 6.62±2.58mm2, 6.33±2.58mm2, p=0.038) from the 3- to the 12-month follow-up. The incidences of uncovered and malapposed struts were low at 3 months and did not significantly change at 6 months and 12 months (3.01±4.43; 2.45±3.75; and 1.47±3.16, p=0.143, and 0.75±0.65; 0.63±0.73; and 0.58±1.42, p=0.162, respectively). Also, frequency of struts with PLIA was already low at three months and significantly decreased during the follow-up (6.4±6.5; 4.6±5.4; and 2.3±3.3, respectively; p=0.001). CONCLUSION Favorable vessel healing was achieved at 3 months after EES implantation without neointimal hyperplasia which was persistently suppressed up to 12 months.

A Case of Quetiapine-related Acute Kidney Injury Requiring Transient Continuous Hemodiafiltration

A 73-year-old man, with congestive heart failure due to combined valvar disease, underwent curative surgery. Although the surgery was successful, his clinical course was eventful because of pulmonary complications, and he began to deteriorate mentally. Quetiapine was prescribed, which appeared to effectively settle his mental status. Following the administration of quetiapine, however, he developed acute kidney injury (AKI) that required continuous hemodiafiltration. Subsequent to discontinuation of quetiapine, his renal function gradually improved. Atypical antipsychotic drugs, including quetiapine, are frequently used to treat delirium in elderly patients in the intensive-care setting. This case highlights a potential risk of quetiapine-related AKI.