Comparison of clinical outcomes following percutaneous coronary intervention versus optimal medical therapy based on gray-zone fractional flow reserve in stable angina patients with intermediate coronary artery stenosis (COMFORTABLE prospective study): Study protocol for a multicenter randomized controlled trial.

BACKGROUND: Even in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called "gray zone," is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values. METHODS/DESIGN: This is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years. DISCUSSION: This is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with "gray zone" FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000031526 . Registered on 1 March 2018.

High-density lipoprotein cholesterol as a therapeutic target for residual risk in patients with acute coronary syndrome.

OBJECTIVE: The current guideline recommends lowering low-density lipoprotein cholesterol (LDL-C) for the primary management of dyslipidemia in patients at high-risk of cardiovascular events. Patients who have achieved LDL-C levels below the recommended targets may still experience cardiovascular events, suggesting additional therapeutic targets beyond LDL-C. The aim of this study was to investigate whether high-density lipoprotein cholesterol (HDL-C) levels had an impact on plaque stabilization in patients with acute coronary syndrome (ACS). METHODS: This study consisted of 90 ACS patients with untreated dyslipidemia. In optical coherence tomography (OCT) analysis, a plaque with fibrous cap thickness ≦160 µm was defined as a high-risk plaque. We registered one high-risk plaque per one patient by baseline OCT imaging, and then administrated high-intensity statin. Based on the follow-up OCT results, patients whose registered plaque was no longer high-risk plaque were classified into a responder group and the remains into a non-responder group. RESULTS: No differences were observed in the baseline LDL-C and HDL-C levels between the two groups. Reduction of LDL-C levels (δ LDL-C: -53 ± 21 mg/dL vs. -42 ± 29 mg/dL, p = 0.036) and increase of HDL-C levels (δ HDL-C: 2.5 ± 5.9 mg/dL vs. -0.3 ± 6.7 mg/dL, p = 0.039) were greater in the responder group. On multivariate logistic regression analysis, δ LDL-C levels (OR: 0.956, 95% CI: 0.921-0.993; p = 0.020) and δ HDL-C levels (OR: 1.143; 95% CI: 1.005-1.300, p = 0.041) were independent contributors for plaque stabilization. CONCLUSIONS: Increase of HDL-C levels is associated with plaque stabilization in patients with ACS. HDL-C could be a therapeutic target for residual risk management.

Optical Coherence Tomography Findings in Patients With Coronary Stent Thrombosis: A Report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).

BACKGROUND: Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We performed a prospective, multicenter study to evaluate OCT findings in patients with ST. METHODS: Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee. RESULTS: Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm2. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1-99.9), 96.6% (92.4-98.5), 34.3% (15.0-60.7), and 9.6% (6.2-14.5) and malapposed struts was 21.8% (8.4-45.6), 8.5% (4.6-15.3), 6.7% (2.5-16.3), and 2.0% (1.2-3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents. CONCLUSIONS: In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.

Resistance to Thyroid Hormone Complicated with Type 2 Diabetes and Cardiomyopathy in a Patient with a TRß Mutation.

Resistance to thyroid hormone (RTH) is a genetic disorder characterized by reduced tissue responsiveness to thyroid hormone. We herein describe a 60-year old man who presented with the clinical features of cardiomyopathy, diabetes mellitus and elevated thyroid hormones with unsuppressed thyroid stimulating hormone. A genetic analysis of thyroid hormone receptor (TR) revealed a missense mutation (A268D) in the TRß gene. Clinical manifestations of RTH may be variable due to different tissue distributions of TR subtypes and different actions of mutant receptors. The current case demonstrates that patients with a TRß mutation may have impaired his glucose metabolism and a reduced cardiac function, although patients appear clinically euthyroid.

Impact of Culprit Plaque and Atherothrombotic Components on Incomplete Stent Apposition in Patients With ST-Elevation Myocardial Infarction Treated With Everolimus-Eluting Stents　- An OCTAVIA Substudy.

BACKGROUND: The role of culprit plaque and related atherothrombotic components on incomplete stent apposition (ISA) occurrence after primary percutaneous coronary intervention (p-PCI) is unknown. METHODS AND RESULTS: ST-segment elevation myocardial infarction (STEMI) patients undergoing p-PCI with an everolimus-eluting stent were prospectively investigated with optical coherence tomography (OCT) of the infarct-related artery before, after stenting and at 9 months. OCT data, aspirated thrombus and serum inflammatory biomarkers were analyzed. 114 patients with 114 lesions were evaluated. Acute ISA occurred in 82 lesions (71.9%), preferentially in larger vessels with a median area of 0.2 mm(2). The presence of thrombus before stent implantation (odds ratio (OR) 5.5, 95% confidence interval (CI) [1.1-26.9], P=0.04) and the lipid content in the target segment (OR 1.3, 95% CI [1.0-1.5], P=0.04) independently predicted acute ISA. At 9-month follow-up, ISA persisted in 46 lesions (56.1%). The volume of acute ISA significantly predicted persistent ISA (OR 1.3, 95% CI [1.1-1.5], P=0.01). Late-acquired ISA occurred in 39 lesions (34.2%) with a median area of 0.3 mm(2). Red/mixed thrombus before stent implantation (OR 3.7, 95% CI [1.0-13.3], P=0.05) and length of the underlying ruptured plaque (OR 1.7, 95% CI [1.1-2.8] P=0.02) were independently associated with late-acquired ISA. CONCLUSIONS: In STEMI patients, culprit plaque and atherothrombotic components of the infarct-related artery significantly contribute to the onset of acute and late ISA. ISA persistence at follow-up depends on the initial volume of acute ISA.

Eroded Versus Ruptured Plaques at the Culprit Site of STEMI: In Vivo Pathophysiological Features and Response to Primary PCI.

OBJECTIVES: The aim of this study was to evaluate the pathophysiological features and response to primary percutaneous coronary intervention (PCI) of nonruptured/eroded plaque versus ruptured plaque as a cause of ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Autopsy series identified nonruptured/eroded plaque and ruptured plaque as the principal pathological substrates underlying coronary thrombosis in STEMI. The real incidence of different plaque morphologies, associated biological factors, superimposed thrombus, and their interaction with primary PCI remain largely unknown. METHODS: In a prospective study, 140 patients with STEMI underwent optical coherence tomography of the infarct-related artery (IRA) before PCI, after everolimus-eluting stent implantation and at 9-month follow-up. Histopathology and immunohistochemistry of thrombus aspirates and serum biomarkers were assessed at baseline. RESULTS: Culprit plaque morphology was adjudicated in 97 patients: 32 plaques (33.0%) with an intact fibrous cap (IFC), 63 (64.9%) plaques with a ruptured fibrous cap (RFC), and 2 (2.1%) spontaneous dissections. Patients with an IFC and RFC had similar clinical characteristics, and serum inflammatory and platelets biomarkers. An IFC presented more frequently with a patent IRA (56.2% vs. 34.9%; p = 0.047), and had fewer lipid areas (lipid-rich areas: 75.0% vs. 100.0%; p < 0.001) and less residual thrombus before stenting (white thrombus: 0.41 mm(3) vs. 1.52 mm(3); p = 0.001; red thrombus: 0 mm(3) vs. 0.29 mm(3); p = 0.001) with a lower peak of creatine kinase-myocardial band (66.6 IU/l vs. 149.8 IU/l; p = 0.025). At the 9-month optical coherence tomography, IFC and RFC had similar high rates of stent strut coverage (92.5% vs. 91.2%; p = 0.15) and similar percentage of volume obstruction (12.6% vs. 10.2%; p = 0.27). No significant differences in clinical outcomes were observed up to 2 years. CONCLUSIONS: In the present study, an IFC was observed at the culprit lesion site of one-third of STEMIs. IFC, compared with RFC, was associated with higher rates of patent IRA at first angiography, fewer lipid areas, and residual endoluminal thrombus. However, no difference in vascular response to everolimus-eluting stent was observed. (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty [OCTAVIA]; NCT01377207).

Comparison of vascular response between everolimus-eluting stent and bare metal stent implantation in ST-segment elevation myocardial infarction assessed by optical coherence tomography.

AIMS: The long-term safety of second-generation everolimus-eluting stents (EESs) in ST-segment elevation myocardial infarction (STEMI) remains unclear. The aim of this study was to evaluate the late vascular response after stent implantation in STEMI between EES and bare-metal stent (BMS) by using optical coherence tomography (OCT). METHODS AND RESULTS: A prospective OCT examination was performed in 102 patients at 10 months after stent implantation for treatment of STEMI. A total of 1253 frames with 12 772 struts in 61 EESs and 776 frames with 8594 struts in 41 BMSs were analysed. There were no significant differences in the percentage of uncovered struts (2.1 ± 2.8 vs. 1.7 ± 2.7%, P = 0.422) and malapposed struts (0.7 ± 1.3 vs. 0.6 ± 1.2%, P = 0.756) between EES and BMS. The frequency of intra-stent thrombus was comparable between the two stents (13 vs. 10%, P = 0.758). The mean neointimal thickness was smaller in EES compared with BMS (104 ± 39 vs. 388 ± 148 µm, P < 0.001). In-segment binary restenosis and target lesion revascularization was less often seen in EES compared with BMS (3 vs. 17%, P = 0.028 and 2 vs. 12%, P = 0.037, respectively). CONCLUSION: When compared with BMS, EES showed a lower rate of stent restenosis, similar frequency of neointimal coverage, stent malapposition, and intra-stent thrombus at 10 months after stent implantation in STEMI. Our results suggest the safety and effectiveness of EES in primary percutaneous coronary intervention for STEMI patients.

Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study.

BACKGROUND: The detailed mechanism of plaque stabilization by statin therapy is not fully understood. OBJECTIVES: The aim of this study was to assess the effect of lipid-lowering therapy with 20 mg/day of atorvastatin versus 5 mg/day of atorvastatin on fibrous cap thickness in coronary atherosclerotic plaques by using optical coherence tomography (OCT). METHODS: Seventy patients with unstable angina pectoris and untreated dyslipidemia were randomized to either 20 mg/day or 5 mg/day of atorvastatin therapy. OCT was performed to assess intermediate nonculprit lesions at baseline and 12-month follow-up. RESULTS: Serum low-density lipoprotein cholesterol level was significantly lower during therapy with 20 mg/day compared with 5 mg/day of atorvastatin (69 mg/dl vs. 78 mg/dl; p = 0.039). The increase in fibrous cap thickness was significantly greater with 20 mg/day compared with 5 mg/day of atorvastatin (69% vs. 17%; p < 0.001). The increase in fibrous cap thickness correlated with the decrease in serum levels of low-density lipoprotein cholesterol (R = -0.450; p < 0.001), malondialdehyde-modified low-density lipoprotein (R = -0.283; p = 0.029), high-sensitivity C-reactive protein (R = -0.276; p = 0.033), and matrix metalloproteinase-9 (R = -0.502; p < 0.001), and the decrease in grade of OCT-derived macrophages (R = -0.415; p = 0.003). CONCLUSIONS: Atorvastatin therapy at 20 mg/day provided a greater increase in fibrous cap thickness in coronary plaques compared with 5 mg/day of atorvastatin. The increase of fibrous cap was associated with the decrease in serum atherogenic lipoproteins and inflammatory biomarkers during atorvastatin therapy. (Effect of Atorvastatin Therapy on Fibrous Cap Thickness in Coronary Atherosclerotic Plaque as Assessed by Optical Coherence Tomography: The EASY-FIT Study; NCT00700037).

Difference of ruptured plaque morphology between asymptomatic coronary artery disease and non-ST elevation acute coronary syndrome patients: an optical coherence tomography study.

BACKGROUND: Autopsy studies have reported that rupture of a thin-cap fibroatheroma and subsequent thrombus formation is the major mechanism leading to acute coronary syndrome (ACS). However, it is not clear why only some plaque ruptures lead to ACS. Optical coherence tomography (OCT) is a high-resolution imaging modality which is capable of investigating detailed coronary plaque morphology in vivo. The objective of this study was to determine whether ruptured plaque morphology assessed by OCT differs between asymptomatic coronary artery disease (CAD) and non-ST elevation acute coronary syndrome (NSTEACS). METHODS: We examined ruptured plaque morphology using OCT in 80 patients, 33 with asymptomatic CAD and 47 with NSTEACS. RESULTS: The frequency of lipid-rich plaque and intracoronary thrombus was significantly lower in asymptomatic CAD than in NSTEACS (61% vs. 85%, p = 0.013 and 9% vs. 83%, p < 0.001, respectively). Although maximal ruptured cavity cross-sectional area (CSA) was similar in both groups, lumen area at the rupture site and minimal lumen area were significantly larger in asymptomatic CAD than in NSTEACS (3.78 ± 1.50 mm(2) vs. 2.70 ± 1.55 mm(2), p = 0.003 and 2.75 ± 0.99 mm(2) vs. 1.72 ± 0.90 mm(2), p < 0.001, respectively). CONCLUSIONS: OCT revealed that the morphology of ruptured plaques differs between asymptomatic CAD and NSTEACS in terms of lumen area and the frequency of lipid-rich plaques and thrombi. These morphological features may be associated with the clinical presentation of CAD.

Acceleration time of systolic coronary flow velocity to diagnose coronary stenosis in patients with microvascular dysfunction.

BACKGROUND: The aim of this study was to test whether acceleration time of systolic coronary flow velocity could contribute to the diagnosis of coronary stenosis in patients with microvascular dysfunction, on the basis of the hypothesis that systolic coronary flow is less influenced by microvascular function because of compressed myocardium. METHODS: Coronary flow velocity was assessed in the left anterior descending coronary artery during hyperemia with intravenous adenosine by echocardiography in 502 patients who were scheduled for coronary angiography because of coronary artery disease and significant valvular disease. Coronary flow velocity reserve (CFVR) and the percentage acceleration time (%AT), as the percentage of the time from the beginning to the peak of systolic coronary flow over systolic time during hyperemia, were calculated. The diagnostic ability of CFVR and %AT for angiographic coronary artery stenosis was then analyzed. As invasive substudies, fractional flow reserve and %AT by a dual-sensor (pressure and Doppler velocity) guidewire were measured simultaneously with %AT on transthoracic echocardiography (n = 14). RESULTS: Patients with coronary stenosis had significantly lower CFVR (1.7 ± 0.4) and greater %AT (65 ± 9%) compared with those without stenosis (2.6 ± 0.6 and 50 ± 13%, respectively). Percentage acceleration time by Doppler echocardiography was in good agreement with %AT (r = 0.98) and fractional flow reserve (r = 0.74) invasively measured by dual-sensor guidewire. Cutoff values of CFVR and %AT were determined as 2.0 and 60% in receiver operating characteristic curve analysis. The sensitivity, specificity, and accuracy of CFVR to detect coronary stenosis were 71.1%, 77.3%, and 75.4%, while those of %AT were 83.4%, 71.8%, and 75.4%, respectively. In addition, %AT provided high accuracy to detect coronary stenosis, especially in patients with previous myocardial infarctions, valvular disease, and left ventricular hypertrophy (81.1%, 84.1%, and 73.4%, respectively). CONCLUSIONS: The %AT of systolic coronary flow velocity is a promising marker to diagnose coronary stenosis in patients with microvascular dysfunction.

Comparison of diagnostic accuracy between multidetector computed tomography and virtual histology intravascular ultrasound for detecting optical coherence tomography-derived fibroatheroma.

Histopathological studies have reported that optical coherence tomography (OCT) can accurately detect fibroatheroma that is involved in not only culprit lesion of acute coronary syndrome but also no-reflow phenomenon after percutaneous coronary intervention. Studies have demonstrated superiority of OCT in plaque characterization and interruption of arterial wall component. At current, multidetector computed tomography (MDCT) and virtual histology intravascular ultrasound (VH-IVUS) are considered as alternative imaging devices for coronary plaque characterization. This study aimed to compare the diagnostic accuracy for detecting fibroatheroma between MDCT and VH-IVUS using OCT as the reference standard. Forty-three lesions from 27 patients assessed by MDCT, VH-IVUS, and OCT were included in this study. Fibroatheroma was defined by OCT as a signal-poor region with a fast signal drop-off and little or no signal backscattering within the lesion. From 43 lesions, OCT revealed 21 fibroatheromas. Ring-like sign assessed by MDCT and positive remodeling assessed by IVUS were more frequently observed in OCT-fibroatheroma than non-OCT-fibroatheroma. The remodeling index of OCT-fibroatheroma assessed by MDCT and IVUS were higher than those of non-OCT-fibroatheroma. The sensitivity, specificity, positive predict values, negative predict values and accuracy of ring-like sign by MDCT and VH-IVUS for detecting OCT-fibroatheroma were 43, 95, 90, 64, 70 % and 71, 45, 56, 63, 58 %, respectively. Our results suggest that both accuracies of MDCT and VH-IVUS to detect OCT-fibroatheroma are insufficient. We need to apply appropriate device for searching vulnerable plaque.

Prognostic value of microvascular resistance index immediately after primary percutaneous coronary intervention on left ventricular remodeling in patients with reperfused anterior acute ST-segment elevation myocardial infarction.

OBJECTIVES: This study sought to investigate the relationship between the degree of microvascular dysfunction assessed by a dual-sensor guidewire (pressure and Doppler velocity) and left ventricular (LV) remodeling after successful primary percutaneous coronary intervention (PPCI) for a first anterior acute myocardial infarction (AMI). BACKGROUND: Microvascular dysfunction after AMI is associated with progressive LV dilation. METHODS: In 24 consecutive patients, the microvascular resistance index (MVRI) immediately after PPCI was calculated as the ratio of the mean distal pressure to average peak flow velocity during maximal hyperemia. Cardiac magnetic resonance was performed to determine LV volumes at baseline and 8-month follow-up. LV remodeling was defined as an increase in left ventricular end-diastolic volume (LVEDV) of ≥20%. RESULTS: In patients with an MVRI greater than the median value of 2.96 mm Hg·cm(-1)·s, the LVEDV increased significantly from 117.1 ± 20.7 ml at baseline to 146.5 ± 21.4 ml (p = 0.006) at 8 months, whereas it did not change between baseline and 8 months (108.2 ± 21.2 ml vs. 111.6 ± 29.9 ml, p = 0.620) in patients with an MVRI ≤2.96 mm Hg·cm(-1)·s. LV remodeling was more frequent in the group with an MVRI >2.96 mm Hg·cm(-1)·s (64% vs. 15%, p = 0.033). Furthermore, there was a positive correlation between MVRI and the percentage of increase or decrease in LVEDV (r = 0.42, p = 0.042). Logistic regression analysis showed that MVRI was the strongest univariate predictor of LV remodeling. The best cutoff value of MVRI was 2.96 mm Hg·cm(-1)·s with a sensitivity of 78% and a specificity of 73%. CONCLUSIONS: MVRI immediately after PPCI predicts LV remodeling in patients with reperfused anterior AMI.

High-density lipoprotein cholesterol level is associated with fibrous cap thickness in acute coronary syndrome.

BACKGROUND: Although low high-density lipoprotein cholesterol (HDL-C) level has been reported as an independent risk factor for coronary artery disease, few studies addressed the direct relationship between the presence of thin-cap fibroatheroma (TCFA) that is considered as vulnerable plaque in pathology and HDL-C level. The aim of this study was to investigate whether lesion vulnerability is related to HDL-C level in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A total of 261 patients with ACS who underwent optical coherence tomography prior to percutaneous coronary intervention, were enrolled. Patients were divided into a TCFA group (n=124) and a non-TCFA group (n=137). TCFA was defined as a lipid plaque (lipid content in ≥1 quadrant) covered with <70 µm-thickness fibrous caps. There were no differences in patient characteristics and clinical results between the 2 groups except for HDL-C level, low-density lipoprotein cholesterol (LDL-C) level, and high-sensitive C-reactive protein (hs-CRP) level. On multivariate regression analysis, low HDL-C level (ß coefficient: 0.302, P<0.001), high LDL-C level (ß coefficient: -0.172, P=0.008), hs-CRP level (ß coefficient: -0.145, P=0.017), and current smoking (ß coefficient: -0.124, P=0.028) were identified as independent contributors to fibrous cap thickness. CONCLUSIONS: HDL-C is correlated with fibrous cap thickness of the culprit lesion in patients with ACS. HDL-C may be considered as a therapeutic target for plaque stabilization.

Coronary superficial and spotty calcium deposits in culprit coronary lesions of acute coronary syndrome as determined by optical coherence tomography.

The characteristics of coronary artery calcium responsible for vulnerable plaque remain incompletely elucidated. We used optical coherence tomography to investigate the characteristics of coronary calcium in acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP). We evaluated calcium deposits in the culprit lesions (30-mm segment) using optical coherence tomography in 187 patients with AMI (n = 44), UAP (n = 73), or SAP (n = 70). The arc, area, and length of calcium were significantly smaller in those with AMI and UAP than in those with SAP (p <0.001). The number of spotty calcium deposits (with an arc of <90°) per patient was significantly larger in the AMI and UAP groups than in the SAP group (p <0.001). The number of large calcium deposits (with an arc of >90°) per patient was significantly lower in the AMI and UAP groups than in the SAP group (p <0.001). The minimum distance between the inner edge of the calcium and the luminal surface was significantly shorter in the AMI and UAP groups than in the SAP group (p <0.001). Plaque rupture frequency correlated positively with the number of spotty calcium deposits (r = 0.479, p <0.001) and inversely with the number of large calcium deposits (r = -0.219, p = 0.003). In conclusion, calcium was very spotty and more superficial in the culprit lesions of AMI and UAP. These characteristics of calcium might play an important role in the pathogenesis of plaque vulnerability.

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.

Difference in neointimal appearance between early and late restenosis after sirolimus-eluting stent implantation assessed by optical coherence tomography.

OBJECTIVES: Late in-stent restenosis (ISR) is an important clinical issue in the drug-eluting stent era. Autopsy studies have reported different underlying mechanisms between early ISR and late ISR. The aim of the present study was to compare the neointimal tissue appearance between early ISR (<1 year) and late ISR (>1 year) after sirolimus-eluting stent (SES) implantation using optical coherence tomography (OCT). MATERIALS AND METHODS: We examined the neointimal tissue appearance in 48 ISR lesions after SES implantation [30 early ISR lesions (8±1 months after stenting) and 18 late ISR lesions (34±14 months after stenting)] by OCT. ISR was defined as percent diameter stenosis more than 50% within the stented segment in angiography. Lipid-rich neointima was characterized by signal-poor regions with diffuse borders. Thin-cap fibroatheroma (TCFA)-like neointima was defined by lipid-rich neointima with cap thickness 65 µm or less. RESULTS: In the OCT findings, heterogeneous neointima was more often observed in the late ISR group compared with the early ISR group (89 vs. 43%, P=0.002). Although the frequency of intraluminal thrombus was not different between the two groups (P=0.085), the frequency of lipid-rich neointima (83 vs. 27%, P<0.001), TCFA-like neointima (39 vs. 10%, P=0.028), microchannels within neointima (67 vs. 27%, P=0.007), and neointimal disruption (33 vs. 3%, P=0.008) was significantly higher in the late ISR group. CONCLUSION: In the present OCT study, it was found that atherosclerotic progression of neointima, such as lipid-rich neointima, TCFA-like neointima, microchannels, and neointimal disruption, was more often observed in late ISR lesions after SES implantation compared with early ISR ones.

Clinical significance of low signal intensity area surrounding stent struts identified by optical coherence tomography.

Previous intravascular ultrasound studies have shown that echolucent neointimal hyperplasia occasionally appears after bare-metal stent (BMS) or sirolimus-eluting stent (SES) implantation. Optical coherence tomography (OCT) studies have also demonstrated that paclitaxel-eluting stent (PES) restenosis exhibited similar images showing low signal intensity areas (LSIA) surrounding stent struts and three-layer appearance (TLA). The aim of the present study was to investigate the clinical significance of LSIA on OCT images in various types of stents. Fifty nine consecutive patients who underwent scheduled follow-up coronary angiography and OCT were enrolled. There was no significant difference in the prevalence of LSIA among the 3 stent groups (BMS 30%, SES 19%, PES 28%, P = 0.70). LSIA thickness was larger in the PES group than in the other stent groups (BMS 0.51 ± 0.21 mm, SES 0.35 ± 0.06 mm, PES 0.87 ± 0.19 mm, P < 0.01). The ratio of LSIA thickness to the neointimal thickness was also larger in PES compared with other stents (BMS 53 ± 9 %, SES 57 ± 8 %, PES 77 ± 5 %, P < 0.01). Also, LSIA thickness in patients with in-stent restenosis (ISR) was significantly larger than in those without ISR (0.37 ± 0.37 mm versus 0.12 ± 0.26 mm, P = 0.048). Our results suggest that LSIA might be involved in excessive neointimal formation, and that the healing response after PES implantation might be different from BMS or SES.

Altered coronary flow velocity reserve and left ventricular wall motion dynamics: a phenomenon in hypertensive patients with ECG strain.

BACKGROUND: The inner-half layer of the left ventricular (LV) wall is primarily affected by ischemia and increased LV afterload. We hypothesized that LV wall thickening of inner-half layer and coronary microvascular function are impaired in hypertensive patients, especially in those with electrocardiographic (ECG) strain, which is a marker of LV hypertrophy and adverse prognosis. Therefore, the aim of this study is to investigate the association of the ratio of inner- to outer-half layer of the LV myocardial deformation and coronary microvascular function with ECG strain in hypertensive patients. METHODS: We studied 98 hypertensive patients and 13 controls. Hypertensive patients were divided into 2 groups, with (S+) and without (S-) ECG strain. Coronary flow velocity reserve (CFVR) of the left anterior descending artery was evaluated using transthoracic echocardiography. Circumferential and radial strains of the LV wall were analyzed by two-dimensional echocardiographic speckle tracking method, and the inner- to outer-half layer ratio (in/out ratio) was assessed. RESULTS: Coronary flow velocity reserve of S+ (2.06 ± 0.65) was significantly smaller than those in S- and controls (3.03 ± 0.65 and 3.38 ± 0.51, respectively). In/out ratio in both circumferential and radial strains were decreased as well as in S+ patients. Furthermore, in/out ratio was directly proportional to CFVR. CONCLUSIONS: Hypertensive patients with ECG strain possessed severely impaired CFVR and inner-half myocardial deformation. Moreover, the more severe the LV hypertrophy progresses, the greater is the impairment of coronary microvascular and LV inner-half myocardial deformation. Thus, CFVR and in/out ratio are useful quantitative markers that can render sensitive assessment of physiological changes in hypertensive heart disease.