Tsuyoshi Nishiguchi

Prevalence of spontaneous coronary artery dissection in patients with acute coronary syndrome

Aims: Spontaneous coronary artery dissection (SCAD) found typically in young females without classical coronary risk factors is thought to be a very rare cause of acute coronary syndrome (ACS). The prevalence of SCAD in ACS subjects has been unclear, probably due to the nature of coronary angiography. The aim of this study was to use optical coherence tomography (OCT) to investigate the prevalence of SCAD in ACS. Methods and results: This study consisted of 326 patients with ACS (with or without ST-segment elevation) who underwent OCT to explore the entire culprit artery. According to OCT findings, patients were divided into a SCAD, a plaque rupture (PR), and a non-SCAD/non-PR group. OCT revealed 13 (4.0%) SCADs and 160 (49.1%) plaque ruptures in ACS subjects. The percentage of females versus males was greater in the SCAD group (SCAD: 53.8% vs. PR: 20.0% vs. non-SCAD/non-PR: 23.5%, p=0.02) while no difference was observed in age (SCAD: 67.3±13.3 vs. PR: 66.5±11.1 vs. non-SCAD/non-PR: 67.0±10.5, p=0.90). The prevalence of dyslipidemia (SCAD: 30.8% vs. PR: 63.8% vs. non-SCAD/non-PR: 67.5%, p=0.03) and current smoking (SCAD: 7.7% vs. PR: 57.9% vs. non-SCAD/non-PR: 59.7%, p<0.01) were significantly lower in the SCAD group. Conclusions: SCAD is not a rare cause for ACS, especially in females without classical coronary risk factors.

MicroRNAs and Cardiovascular Diseases

Coronary artery diseases (CAD) and heart failure have high mortality rate in the world, although much progress has been made in this field in last two decades. There is still a clinical need for a novel diagnostic approach and a therapeutic strategy to decrease the incidence of CAD. MicroRNAs (miRNAs) are highly conserved noncoding small RNA molecules that regulate a large fraction of the genome by binding to complementary messenger RNA sequences, resulting in posttranscriptional gene silencing. Recent studies have shown that specific miRNAs are involved in whole stage of atherosclerosis, from endothelium dysfunction to plaque rupture. These findings suggest that miRNAs are potential biomarkers in early diagnosis and therapeutic targets in CAD. In the present review, we highlight the role of miRNAs in every stage of atherosclerosis, and discuss the prospects of miRNAs in the near future.

Long-Term Outcome After Deferral of Revascularization in Patients With Intermediate Coronary Stenosis and Gray-Zone Fractional Flow Reserve

BACKGROUND A strategy of deferred percutaneous coronary intervention for coronary stenosis with fractional flow reserve (FFR) 0.75-0.80, termed the gray zone, remains a matter of debate. The aim of this study was to assess the safety of deferring revascularization for patients with FFR 0.75-0.80 compared with those with FFR >0.80. METHODS AND RESULTS We assessed 3-year clinical outcome in 150 patients with angiographically intermediate stenosis who had revascularization deferred on the basis of FFR ≥ 0.75 (FFR 0.75-0.80, n=56; FFR >0.80, n=94). Target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR) was evaluated during follow-up. Cardiac death was observed in 1 patient with FFR 0.75-0.80. There was no target vessel-related MI in either group. The incidence of ischemia-driven TVR was higher in patients with FFR 0.75-0.80 than in those with FFR >0.80 (14% vs. 3%, P=0.020). TVF-free survival was significantly worse for the patients with FFR 0.75-0.80 than those with FFR >0.80 (hazard ratio, 5.2; 95% confidence intervals: 1.4-19.5; P=0.015). CONCLUSIONS Patients with FFR 0.75-0.80 were at higher risk of TVF mainly due to TVR than those with FFR >0.80.

Distribution, frequency and clinical implications of napkin-ring sign assessed by multidetector computed tomography

BACKGROUND Plaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). Plaques showing the napkin-ring sign in multidetector computed tomography (MDCT) have been reported as thin-cap fibroatheroma that is recognized as a precursor lesion for plaque rupture. The purpose of this study was to investigate distribution and frequency of napkin-ring sign and its relationship to features indicating coronary plaque vulnerability on MDCT in patients with coronary artery disease. METHODS We enrolled 273 patients with ACS (n=61) or stable angina pectoris (SAP, n=212) who were assessed by MDCT. The definition of the napkin-ring sign was the presence of a ring of high attenuation and the CT attenuation of a ring presenting higher than those of the adjacent plaque and no greater than 130HU. RESULTS The culprit plaques with the napkin-ring sign show higher remodeling index and lower CT attenuation (1.15±0.12 vs. 1.02±0.12, p<0.01 and 39.9±22.8 vs. 72.7±26.6, p<0.01, respectively). Napkin-ring sign at culprit lesions was more frequent in patients with ACS than those with SAP (49.0% vs. 11.2%, p<0.01). Moreover, napkin-ring sign at non-culprit lesions was more frequently observed in ACS patients compared with SAP patients (12.7% vs. 2.8%, p<0.01). The distribution of the napkin-ring sign in the right coronary arteries and left circumflex arteries of our population was relatively even, whereas the napkin-ring sign in the left anterior descending artery was common in the proximal sites (p<0.01). CONCLUSIONS The napkin-ring sign assessed by MDCT represents similar clinical features of fibroatheroma. MDCT could contribute to the search for fibroatheroma.

Optical Coherence Tomography Predictors for Edge Restenosis After Everolimus-Eluting Stent Implantation

Background—Stent edge restenosis (SER) remains a potential limitation of drug-eluting stents. The aim of this study was to determine optical coherence tomography (OCT) predictors for angiographic late SER after everolimus-eluting stent implantation. Methods and Results—We retrospectively analyzed 319 patients who underwent OCT immediately after everolimus-eluting stent implantation and scheduled 9- to 12-month follow-up angiography. The binary angiographic SER rate was 10% (32/319) in the patients, 8.4% (32/382) in lesions, and 4.4% (33/744) in stent edge segments. In the stent edge segments at post stenting, OCT-derived lipidic plaque (61% versus 20%; P<0.001) was more often observed in the SER group, and OCT-measured minimum lumen area (4.13±2.61 versus 5.58±2.46 mm2; P=0.001) was significantly smaller in the SER group compared with the non-SER group. Multivariate analysis identified lipidic plaque (odds ratio: 5.99; 95% confidence interval: 2.89–12.81; P<0.001) and minimum lumen area (odds ratio: 0.64; 95% confidence interval: 0.42–0.96; P=0.029) as independent predictors of binary SER. Receiver-operating characteristic analysis demonstrated that lipid arc of 185° (sensitivity: 71%; specificity: 72%; area under the curve: 0.761) and minimum lumen area of 4.10 mm2 (sensitivity: 67%; specificity: 77%; area under the curve: 0.787) were optimal cutoff values for predicting ischemia-driven SER. Conclusions—The present OCT study demonstrated that lipidic plaque and minimum lumen area in the stent edge segments at post stenting were associated with late SER after everolimus-eluting stent implantation. OCT provides valuable information to determine an appropriate landing zone for stent implantation.

Feasibility of Optical Coronary Tomography in Quantitative Measurement of Coronary Arteries With Lipid-Rich Plaque

BACKGROUND The aim of the present study was to evaluate the feasibility of optical coherence tomography (OCT) for measurement of vessel area in coronary arteries with lipid-rich plaque as compared with intravascular ultrasound (IVUS). METHODS AND RESULTS: We investigated 80 coronary artery segments with lipid-rich plaque on OCT and non-attenuated plaque on IVUS. According to the lipid arc on OCT, the plaques were classified into 4 groups: group 1, lipid arc ≤90°; group 2, 90°270°. Vessel circular arcs that could not be identified due to OCT signal attenuation were interpolated using an approximating algorithm. OCT-measured vessel area was well-correlated with IVUS-measured vessel area (R=0.834, P<0.001). On Bland-Altman plot, there was a good agreement between OCT-measured vessel area and IVUS-measured vessel area, although mean difference and limits of agreement increased with increase of lipid arc (mean difference in groups 1-4: -0.21, -0.31, -1.02, and -2.13 mm(2); lower limit: -1.49, -3.22, -5.24, and -9.25 mm(2); and upper limit: 1.07, 2.60, 3.20, and 4.99 mm(2)). Intra-observer (R=0.97-0.99, P<0.001) and inter-observer (R=0.97-0.99, P<0.001) reproducibility for OCT measurement of vessel area was excellent. CONCLUSIONS Like IVUS, OCT can be used to measure vessel area in coronary arteries with lipid-rich plaque.

Very Late Stent Thrombosis After Drug-Eluting Stent in Segment With Neointimal Tissue Coverage

Although drug-eluting stents have dramatically reduced restenosis, late stent thrombosis (LST) remains a clinical problem. While stent thrombosis is a multifactorial process, at least 1 pathologic study has shown that the extent of the stent coverage (the ratio of uncovered struts to total struts)

Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment–Elevation Myocardial Infarction

Objective—Early clinical presentation of ST-segment–elevation myocardial infarction (STEMI) and non–ST-segment–elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. Approach and Results—This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9–73.2] ng/mL versus prestent local, 69.1 [32.2–152.3] ng/mL versus poststent local, 68.0 [35.6–133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in patients with STEMI (STEMI, 109.9 [54.5–197.8] ng/mL versus non-STEMI: 52.9 [33.0–79.5] ng/mL; stable angina pectoris, 28.3 [14.2–40.0] ng/mL; P<0.01), whereas no difference was observed in the myeloperoxidase level. Poststent local MMP-9 and the presence of red thrombus are the independent determinants for STEMI in multivariate analysis. Conclusions—Local MMP-9 level could determine the early clinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention.

Optical coherence tomography assessment of efficacy of thrombus aspiration in patients undergoing a primary percutaneous coronary intervention for acute ST-elevation myocardial infarction.

ObjectiveWe used optical coherence tomography (OCT) to assess the impact of thrombus aspiration before angioplasty on poststenting tissue protrusions in patients undergoing a primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Methods and resultsA total of 188 patients with STEMI who underwent thrombus-aspiration PCI (n=113) or standard PCI (n=75) were examined in this study. OCT was performed immediately after primary PCI to assess lesion morphology in the stented segment. The minimum stent area was similar between the thrombus-aspiration PCI group and the standard PCI group [7.4 interquartile range (IQR): 5.8–9.4 vs. 7.4 IQR: 5.8–8.9 mm2, P=0.788]. The maximum tissue protrusion area [0.6 (IQR: 0.3–1.1) vs. 1.2 (IQR: 0.8–1.9) mm2, P<0.001], the mean tissue protrusion area [0.1 (IQR: 0.1–0.2) vs. 0.5 (IQR: 0.3–0.8) mm2, P<0.001], and tissue protrusion volume [2.3 (IQR: 1.3–4.3) vs. 8.3 (IQR: 5.4–14.6) mm3, P<0.001] were significantly smaller in the thrombus-aspiration PCI group compared with the standard PCI group. Minimum lumen area was significantly greater in the thrombus-aspiration PCI group compared with the standard PCI group [6.9 (IQR: 5.4–8.8) vs. 6.3 (IQR: 4.6–7.8) mm2, P=0.033]. ConclusionThrombus aspiration before angioplasty in patients with STEMI was associated with significantly smaller tissue protrusion and larger lumen poststenting compared with standard PCI. Thrombus aspiration in primary PCI favorably influenced lesion morphologies in the stented segment.

Association between P-selectin glycoprotein ligand-1 and pathogenesis in acute coronary syndrome assessed by optical coherence tomography

OBJECTIVE Although monocytes appear to be actively involved in the onset of acute coronary syndrome (ACS), they are heterogenous in human peripheral blood. How up-regulation of monocyte subsets leads to coronary plaque rupture followed by thrombus formation remains unclear. Recent studies have shown that P-selectin glycoprotein ligand-1 (PSGL-1) is involved in monocyte activation in patients with thrombus formation. We therefore investigated the relationship between the expression of PSGL-1 on monocyte subsets and thrombus formation using frequency-domain optical coherence tomography (FD-OCT) in patients with ACS. METHODS We enrolled a total of 100 individuals in this study: patients with acute myocardial infarction (AMI, n=25), unstable angina pectoris (UAP, n=20), or stable angina pectoris (n=35) who underwent coronary angiography, and control subjects (n=20). Three monocyte subsets (CD14++CD16-, CD14++CD16+, and CD14+CD16+) and the expression of PSGL-1 were measured by flow cytometry. In patients with AMI and UAP, FD-OCT was performed before percutaneous coronary intervention. RESULTS Circulating peripheral CD14++CD16+ monocytes expressed PSGL-1 more frequently than CD14++CD16- and CD14+CD16+ monocytes in patients with ACS. The expression of PSGL-1 on circulating peripheral CD14++CD16+ monocytes was significantly elevated in patients with AMI compared with the other 3 groups. Moreover, the expression levels of PSGL-1 on CD14++CD16+ monocytes were significantly higher in patients with plaque rupture or intracoronary thrombus assessed by FD-OCT. CONCLUSION Up-regulation of PSGL-1 on CD14++CD16+ monocytes may be a crucial role in plaque rupture and thrombus formation.