Michiya Kageyama

Evaluation of Serial Changes in Tissue Characteristics During Statin-Induced Plaque Regression Using Virtual Histology-Intravascular Ultrasound Studies

Treatment of all coronary arteries is important to improve the prognosis of acute coronary syndrome after early reperfusion of the culprit lesion. Early statin treatment has been reported to cause regression of plaques away from the site of the culprit lesion in patients with acute coronary syndrome. However, the precise mechanism of coronary plaque regression is not well understood. We studied the effects of statins on the regression of coronary plaques away from the culprit lesions in 120 patients with acute coronary syndrome. We used virtual histology-intravascular ultrasound studies to evaluate nonpercutaneous coronary intervention lesions at admission and short-term (2 to 3 weeks) and medium-term (8 to 10 months) follow-up. According to the medium-term evaluation findings, the subjects were divided into 2 groups: a plaque regression group (n = 94) and a plaque progression group (n = 26). In the regression group, the fibrofatty component had decreased at the short-term (-20.0% vs baseline) and had decreased further at the medium-term (-26.7%) evaluations. The fibrous component had also decreased at the short-term (-5.1%) and medium-term (-8.5%) evaluations. In contrast, the necrotic core component showed a tendency to increase in the short term (+12.5%) but then decreased at the medium-term evaluation (-6.3%). In the progression group, the fibrofatty and fibrous components had increased at the short-term (+37.5%, +11.3%) and medium-term (+50.5%, +13.2%) evaluations; however, the necrotic core had decreased at the short-term (-19.0%) and medium-term (-23.8%) evaluations. In conclusion, regarding the course of coronary plaque regression by statin therapy, the plaques began to reduce the volume of fibrofatty and fibrous components in the early phase, associated with a transiently increased necrotic core component. Furthermore, even in the case of plaque progression, statins caused a reduction in the necrotic core.

Clinical features of spontaneous coronary artery dissection

BACKGROUND Spontaneous coronary artery dissection (SCAD) is an infrequent but increasingly recognized cause of acute coronary syndrome (ACS). Previous case reports demonstrated that this condition occurs in young females with a low atherosclerotic risk factor burden and may be associated with peripartum or postpartum status. The purpose of this study was to review patients with angiographically confirmed SCAD to provide additional insight into the diagnosis and treatment of this condition. METHODS AND RESULTS We screened medical records of all patients with ACS from March 2001 to November 2012. From these patients, we selected patients with SCAD based on coronary angiographic review. Of a total of 1159 ACS patients, 10 patients (0.86%) were diagnosed with SCAD. The mean age of these patients was 46 years, and 9 were female. ST-elevation myocardial infarction (STEMI) was observed in 9 patients and 5 patients had no coronary risk factors. One patient was treated conservatively with medication alone and 3 patients underwent thrombectomy. Balloon angioplasty was performed in 2 patients, and a bare metal stent was placed in one of these patients later. In the remaining 4 patients, bare metal stents were implanted emergently. Follow-up coronary angiography showed appropriate repair of SCAD in all 10 patients. CONCLUSIONS In our experience, the clinical features of SCAD appear to be similar to those reported previously. SCAD appears to be rare, but it should be considered in ACS patients, especially in younger females.

Late-phase inflammatory response as a feature of in-stent restenosis after drug-eluting stent implantation.

ObjectivesThe aim of this study was to compare pathological features among in-stent restenosis lesions after drug-eluting stent (DES) placement, those after bare metal stent (BMS) placement, and de-novo atherosclerotic lesions. BackgroundRestenosis after stenting is an over-reaction of the wound-healing response after vascular injury, which is characterized by a sequence of inflammation, granulation, extracellular matrix remodeling, and smooth muscle cell proliferation and migration. Recent advances in DES technology could considerably succeed in inhibiting this sequence of events. Thus, we hypothesized that the mechanism of in-stent restenosis after DES stenting might be different from that after BMS stenting as well as atherosclerosis. MethodsTissues obtained by directional atherectomy (DES: seven specimens, BMS: 17 specimens, and de-novo: 15 specimens) were immunostained for T lymphocytes (CD45), macrophages (CD68), smooth muscle cells (&agr;-smooth muscle actin), endothelial cells (von Willebrand factor), and activated platelets (P-selectin). ResultsThe accumulation of T lymphocytes tended to increase and that of macrophages increased significantly in the DES lesions compared with BMS lesions. No significant differences were observed for the other parameters evaluated. ConclusionPathological features of restenotic tissues after DES implantation showed a stronger inflammatory response compared with those after BMS implantation. Thus, the mechanism of restenosis after DES implantation may be different from that observed after BMS implantation.

The late-phase inflammatory response after drug-eluting stent implantation

Recent advances in drug-eluting stent (DES) technology have succeeded in preventing restenosis. In addition to inhibiting smooth muscle cell proliferation, DES greatly inhibits the local inflammatory response in the acute phase after implantation, leading to prevention of restenosis. However, a unique issue in DES implantation is an impairment of reendothelialization, which may result in abnormal wound healing. Consequently, a late-phase inflammatory relapse could appear in the long term after DES implantation. In this study, we measured serum levels of inflammatory markers, including interleukin (IL)-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, matrix metalloproteinase-9, and myeloperoxidase, as well as high-sensitivity C-reactive protein at follow-up coronary angiography (mean 9 months) in 54 patients who received DES stenting who did not experience restenosis, and compared them with 51 patients receiving bare-metal stents (BMS) without restenosis. The level of IL-6 was over the measurement threshold (≥2.22 pg/ml) in 12 patients (21 %) in the DES group, but in only 2 patients (4 %) in the BMS group (P = 0.003). IL-8 was significantly higher in the DES group than in the BMS group (4.51 ± 2.40 vs 3.84 ± 1.34 pg/ml, P = 0.015). The levels of other biomarkers were similar between the two groups. DES showed an increase in inflammatory cytokines in the late phase after implantation in comparison with patients who received BMS, suggesting late-stage inflammation. Therefore, the wound-healing response after DES implantation might be different from that after BMS.

Which has the stronger impact on coronary artery disease, eicosapentaenoic acid or docosahexaenoic acid?

It has been suggested that n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against cardiovascular diseases, and EPA/arachidonic acid (AA) and DHA/AA ratios in serum are potential risk markers for coronary artery disease (CAD). The purpose of this study was to clarify the clinical significance of the difference in the EPA/AA ratio and the DHA/AA ratio in patients with CAD. In 369 patients with confirmed or suspected CAD who underwent diagnostic coronary angiography, we measured serum levels of EPA, DHA and AA and calculated the EPA/AA and DHA/AA ratios. The EPA/AA ratio was significantly lower in patients with acute coronary syndrome (ACS) than in patients with chronic CAD or chest pain syndrome (0.27±0.19 vs. 0.44±0.20, respectively; P<0.01), whereas the DHA/AA ratio was similar in the two groups (0.78±0.27 vs. 0.79±0.37). Multiple logistic regression analyses using various biomarkers related to coronary risk discriminated ACS from other disease entities and demonstrated that the EPA/AA ratio (odds ratio: 0.0012, 95% confidence interval: 0.00–0.16, P<0.01) but not the DHA/AA ratio (odds ratio: 1.05, 95% confidence interval: 0.98–1.12) was a significant independent predictive factor. Our findings suggest that the EPA/AA ratio might be more closely associated with the pathophysiology of CAD, especially with that of ACS, than the DHA/AA ratio. Our findings suggest that interventions with EPA agents or supplemental EPA intake, compared with DHA agents or supplemental DHA, may confer greater benefit for plaque stabilization to prevent the onset of ACS in patients with CAD.

Pathological features of in-stent restenosis after sirolimus-eluting stent versus bare metal stent placement

A 70-year-old man developed diffuse restenosis in the right coronary artery, in which a bare metal stent (BMS) and two sirolimus-eluting stents (SES) were deployed sequentially. He underwent directional coronary atherectomy (DCA) for in-stent restenosis (ISR) lesions 13 months after both BMS and SES stenting. Further 4 months later, that is, 17 months after stent implantation, however, ISR recurred just at the SES site alone. Then we performed second DCA for the ISR lesion at SES site. The tissue materials obtained from debulking were compared histologically. In the first DCA specimen, accumulation of inflammatory cells such as T lymphocytes and macrophages was observed densely in ISR lesions at SES site but not in those at BMS site, and endothelial coverage was absent in ISR lesions at SES site but present in those at BMS site. In the second DCA specimen, ISR lesions at SES site showed less inflammatory cells, compared with first DCA specimen. ISR lesions after drug-eluting stenting showed persistent signs of delayed or incomplete wound healing and relapsed inflammation, compared with BMS. Thus, the mechanism of restenosis after drug-eluting stenting may be different from that after BMS placement.

The different features of angiographic peri-stent contrast staining after implantation of sirolimus-eluting stents

If we had a case with angiographic peri‐stent contrast staining(PSS)s after the first‐generation sirolimus‐eluting stent, we need a further observation using coronary imaging modalities to evaluate the risk of very late stent thrombosis due to PSSs and to continue or to resume the dual antiplatelet therapy if necessary.

Percutaneous Coronary Intervention for Spontaneous Coronary Artery Dissectionunder Intravascular Ultrasound Guidance

Percutaneous Coronary Intervention for Spontaneous Coronary Artery Dissection under Intravascular Ultrasound Guidance A 77-year-old woman underwent percutaneous coronary intervention (PCI) for a spontaneous coronary artery dissection (SCAD) lesion in right coronary artery. A guide wire was advanced to the dissecting lesion, but it was inserted into false lumen. Therefore, we advanced an intravascular ultrasound (IVUS) catheter over the false lumen guide wire. The IVUS observation from the false lumen was useful for navigating the second guide wire into the true lumen. Finally, 38 mm everolimus-eluting stent was successfully placed in the dissecting lesion with fully coverage. The IVUS guidance such as in this case would be promising for the PCI in SCAD case.