Associations of coronary plaque characteristics by integrated backscatter intravascular ultrasound with detectability of vessel external elastic lamina using optical frequency domain imaging in human coronary arteries: A sub-analysis of the MISTIC-1 trial.

OBJECTIVES: We sought to examine associations between plaque characteristics by intravascular ultrasound (IVUS) and detectability of external elastic lamina (EEL) by optical frequency domain imaging (OFDI) in human coronary arteries. BACKGROUND: It is often challenging to detect EEL which represents vessel size by light-based imaging modalities due to light intensity attenuation through atherosclerotic plaque. METHODS: IVUS and OFDI prior to stent implantation were sequentially investigated per protocol. We identified corresponding cross-sections by minimum lumen area (MLA) or just distally to side branches as anatomical landmarks. Plaque characterization was determined by integrated backscatter IVUS analysis. We categorized detectable EEL arc by OFDI into four groups: 0≤ and <1 quadrant (group 1), 1≤ and <2 quadrants (group 2), 2≤ and <3 quadrants (group 3), or 3≤ and <4 quadrants (group 4). RESULTS: We prospectively studied 103 vessels in 93 patients with stable coronary artery disease. Corresponding 711 cross-sections were analyzed. Cross-sections with detectable EEL arc <2 quadrants (group 1 or 2) were observed in 86.1% of MLA sites but only in 29.3% of non-MLA sites (p < .05). Percentage plaque area (%PA) appeared to be the strongest predictor to detect EEL arc <2 quadrants with the cut-off of 60.3% (AUC 0.90; sensitivity 79.8%, specificity 85.5%). Lipid pool and calcification remained statistically significant in predicting detectable EEL arc <2 quadrants after adjustment with %PA. CONCLUSIONS: Presence of large plaque burden, lipid pool, and calcification significantly predicts the detectability of EEL by OFDI assessment. Locations with detectable EEL arc <2 quadrants should thus be avoided for optimal stent landing zone.

Production of Molecular Iodine and Tri-iodide in the Frozen Solution of Iodide: Implication for Polar Atmosphere.

The chemistry of reactive halogens in the polar atmosphere plays important roles in ozone and mercury depletion events, oxidizing capacity, and dimethylsulfide oxidation to form cloud-condensation nuclei. Among halogen species, the sources and emission mechanisms of inorganic iodine compounds in the polar boundary layer remain unknown. Here, we demonstrate that the production of tri-iodide (I3(-)) via iodide oxidation, which is negligible in aqueous solution, is significantly accelerated in frozen solution, both in the presence and the absence of solar irradiation. Field experiments carried out in the Antarctic region (King George Island, 62°13'S, 58°47'W) also showed that the generation of tri-iodide via solar photo-oxidation was enhanced when iodide was added to various ice media. The emission of gaseous I2 from the irradiated frozen solution of iodide to the gas phase was detected by using cavity ring-down spectroscopy, which was observed both in the frozen state at 253 K and after thawing the ice at 298 K. The accelerated (photo-)oxidation of iodide and the subsequent formation of tri-iodide and I2 in ice appear to be related with the freeze concentration of iodide and dissolved O2 trapped in the ice crystal grain boundaries. We propose that an accelerated abiotic transformation of iodide to gaseous I2 in ice media provides a previously unrecognized formation pathway of active iodine species in the polar atmosphere.

Thin cap fibroatheroma defined as lipid core abutting lumen (LCAL) on integrated backscatter intravascular ultrasound - comparison with optical coherence tomography and correlation with peri-procedural myocardial infarction.

BACKGROUND: This study evaluated the ability of a newly developed integrated backscatter intravascular ultrasound (IB-IVUS) system (VISIWAVE, Terumo, Tokyo, Japan) to detect optical coherence tomography (OCT)-verified thin cap fibroatheroma (TCFA) and assessed the correlation with peri-procedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI). METHODS AND RESULTS: One hundred culprit lesions in 100 consecutive patients with ischemic heart disease who consented to repeated IVUS and OCT prior to PCI were studied. Of 100 lesions, 48 had OCT-verified TCFA with a cap thickness <65 µm. Such lesions had larger percentage lipid area and lipid angle >2 quadrants on IB-IVUS. A lipid core abutting lumen (LCAL) was defined as a lipid core pool in the plaque area, directly contacting with the lumen regardless of its circumferential extension. IB-IVUS-identified TCFA defined as a combination of percentage lipid area ≥53.6%, remodeling index ≥1.03, and the presence of LCAL was the best predictor of OCT-verified TCFA with sensitivity, specificity, positive and negative predictive values, and accuracy of 72.9%, 90.4%, 87.5%, 78.3%, and 82.0%, respectively. IB-IVUS-identified TCFA as well as OCT-verified TCFA were significant independent predictors of PMI, after adjusting for other predictors on multivariate analysis. CONCLUSIONS: IB-IVUS can be used to identify plaques with a high prevalence of TCFA. Such techniques can therefore potentially be used to identify lesions with an elevated risk of PMI after PCI.

Pre-procedural glucose levels and the risk for contrast-induced acute kidney injury in patients undergoing emergency coronary intervention.

BACKGROUND: The incidence, risk factors, and outcome of contrast-induced acute kidney injury (CI-AKI) in 730 patients with acute coronary syndrome (ACS) undergoing emergency percutaneous coronary intervention (PCI), whose contrast volume was below maximum allowable contrast dose (MACD) was prospectively investigated. METHODS AND RESULTS: MACD was defined as (5ml×body weight [kg]/baseline creatinine [mg/dl]). CI-AKI was defined as a greater than 25% increase in creatinine from the baseline or an absolute increase of ≥0.5mg/dl within 48h after the procedure. CI-AKI occurred in 212 (29%) patients. Patients with CI-AKI had a higher risk for in-hospital mortality (9.4% vs. 1.5%, P<0.001) and a longer stay in the coronary care unit (median, 4.0 vs. 3.0 days, P<0.001) compared with those without CI-AKI. In a multivariate logistic analysis including 20 clinical variables, elevated glucose levels as variables categorized into quartiles were independently (P<0.001) associated with the development of CI-AKI. In addition, this relationship was seen in both the subgroup of patients with known diabetes and that of those without known diabetes. CONCLUSIONS: CI-AKI might occur commonly and could be be associated with a more complicated clinical course in ACS patients undergoing emergency PCI whose contrast volume does not exceed MACD. Elevated pre-procedural glucose might be a powerful and independent risk factor for the development of CI-AKI in this population.

Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction.

OBJECTIVE: High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern molecule, which suggests a potential role of this protein in the pathophysiology of acute coronary syndrome (ACS). Circulating HMGB1 has been shown to be independently associated with cardiac mortality in ST-segment elevation myocardial infarction. However, its prognostic value remains unclear in unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). METHODS: HMGB1, high-sensitivity C-reactive protein (hsCRP), cardiac troponin I and B-type natriuretic peptide concentrations were measured on admission in 258 consecutive patients (mean age of 67 years) hospitalized for UA/NSTEMI within 24h (mean, 7.4h) of the onset of chest symptoms. RESULTS: A total of 38 (14.7%) cardiovascular deaths, including 10 in-hospital deaths, occurred during a median follow-up period of 49 months after admission. In a stepwise Cox regression analysis including 19 well-known clinical predictors of ACS, HMGB1 [relative risk (RR) 3.24 per 10-fold increment; P = 0.0003], cardiac troponin I (RR 1.83 per 10-fold increment, P = 0.0007), Killip class>1 (RR 4.67, P = 0.0001) and age (RR 1.05 per 1-year increment, P = 0.03), but not hsCRP, were independently associated with cardiovascular mortality. In-hospital and cardiovascular mortality rates were higher in patients with increased HMGB1 (≥ 2.4 ng/mL of median value) than those without increased HMGB1 (6.3% vs. 1.5%, P = 0.04; and 23% vs. 6.9%, P = 0.0003). CONCLUSION: Circulating concentration of HMGB1 on admission may be a potential and independent predictor of cardiovascular mortality in patients hospitalized for UA/NSTEMI within 24h of onset.

Impact of statin therapy on plaque characteristics as assessed by serial OCT, grayscale and integrated backscatter-IVUS.

OBJECTIVES: The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. BACKGROUND: Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics. METHODS: Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months. RESULTS: Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 µm, 189 ± 46 µm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 µm, 142 ± 36 µm; p = NS). Differences in the changes in the percentage lipid volume index (-6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 µm vs. 2 ± 22 µm, p < 0.001) over time between the pitavastatin and diet groups were highly significant. CONCLUSIONS: Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.

Coronary CT angiographic characteristics of culprit lesions in acute coronary syndromes not related to plaque rupture as defined by optical coherence tomography and angioscopy.

AIMS: Pathological and clinical optical coherence tomography (OCT) studies have indicated that acute coronary syndrome (ACS) lesions have either ruptured fibrous caps (RFC-ACS) or intact fibrous caps (IFC-ACS). Although computed tomographic (CT) angiographic characteristics of RFC-ACS include low-attenuation plaques and positive plaque remodelling, features associated with IFC-ACS have not been previously described. The aim of this study was to assess the CT characteristics of IFC-ACS lesions. METHODS AND RESULTS: Seventy-four patients with ACS/stable angina consented to multimodality imaging, of which 66 underwent CT angiography. Of these, 57 culprit lesions in 57 patients were evaluated with sufficient image quality from all four of OCT, angioscopy, intravascular ultrasound, and CT angiography. Intraluminal thrombus was assessed by OCT/angioscopy, and culprit lesions further classified by OCT-based demonstration of fibrous cap integrity. Of 35 culprit lesions with ACS, OCT revealed IFC with thrombus in 10 (29%) and RFC in the remaining 25 (71%); all 22 lesions with stable angina had intact fibrous caps. Fibrous caps were significantly thinner in RFC-ACS than IFC-ACS and stable angina (45 ± 12, 131 ± 57, and 321 ± 146 µm, respectively; P = 0.001). CT angiography revealed that low-attenuation plaques were more frequently observed in RFC-ACS than IFC-ACS and stable angina (88, 40, and 18%; P = 0.001) lesions. Similarly, positive remodelling was more predominantly seen in RFC-ACS than IFC-ACS and stable angina (96, 20, and 14%; P = 0.001). However, none of the specific CT angiography features clearly distinguished IFC-ACS from stable lesions. CONCLUSION: In contrast to the situation with RFC-ACS, distinct culprit lesion characteristics associated with non-rupture-related mechanisms are not identified by CT angiography. It will therefore not be possible to differentiate plaques likely to develop IFC-ACS from stable plaques.

Prediction of the no-reflow phenomenon during percutaneous coronary intervention using coronary computed tomography angiography.

Coronary computed tomography angiography (CTA) can assess plaque characteristics and plaque size noninvasively. The purpose of this study was to investigate whether coronary CTA before percutaneous coronary intervention (PCI) can predict the no-reflow phenomenon during PCI. Seventy-eight patients [acute coronary syndrome (ACS) = 43, stable angina pectoris (SAP) = 35, male/female = 72/6, age: 65 ± 10 years] who underwent 16- or 64-slice CTA in the 4 weeks before PCI were enrolled. The low attenuation plaque size on CTA was compared between patients with (NR+) and without the no-reflow phenomenon (NR-). No-reflow phenomenon was observed in 11 patients, including 10 patients with ACS and 1 patient with SAP. Low attenuation plaque was detected in 9 (82%) NR(+) lesions and 35 (52%) NR(-) lesions. The length of low attenuation plaque was significantly longer in NR(+) than in NR(-) patients (9.0 ± 6.5 vs. 1.6 ± 2.7 mm, p < 0.0001). On step-wise regression analysis, ACS (p = 0.036, 95% CI = 0.009-0.258) and the presence of low attenuation plaque with a length >4.7 mm (p < 0.001, 95% CI = 0.447-0.778) were significant independent predictors of NR(-) no-reflow phenomenon. Low attenuation plaque with lesion length of >4.7 mm on coronary CTA and ACS were the significant predictors for the no-reflow phenomenon during PCI. Coronary CTA assessment before PCI would be useful to predict coronary events during PCI in advance.

Do drug elution components increase the risk of fracture of sirolimus-eluting stents?

OBJECTIVES: Stent fracture (SF) of sirolimus-eluting stents (SES) has emerged recently in the literature and shown to be associated with an increased risk of restenosis; however, little is known regarding SF after bare-metal stent implantation. We sought to assess whether the use of SES was associated with an increased risk of SF compared with its bare-metal platform, the Bx-velocity stent (BX-BMS). METHODS: A total of 478 lesions in 416 patients undergoing SES implantation and subsequent angiography 6-9 months after the index procedure were compared with 152 lesions in 142 consecutive patients treated with BX-BMS. Stented lesions with total stent-length greater than 40 mm were excluded. RESULTS: There were no significant differences in overall baseline clinical and anatomic features between the SES and BX-BMS groups, or in SF frequencies at 6-9 month follow-up (4.4% for SES and 1.3% for BX-BMS, P= 0.078). In-stent restenosis was observed more often in SF lesions versus non-SF lesions (34.8 vs. 7.7%, P< 0.001) in association with a higher 3-year adverse events rate (27.3 vs. 13.6%, P = 0.076). The risk of SF at 6-9 months was independently associated with total stent length [odds ratio (OR), 2.13; 95% confidence interval (CI), 1.18-3.83; P = 0.012], angulated lesions (OR, 4.25; 95% CI, 1.80-10.00; P = 0.001), and right coronary artery lesions (OR, 3.55; 95% CI, 1.46-8.62; P = 0.005) but not with SES use. CONCLUSION: Stent implantation in right coronary artery lesions, tortuous lesions, and/or longer lesions covered with longer stents, and not SES versus BX-BMS use, may be associated with increased likelihood of SF.

The fate of incomplete stent apposition with drug-eluting stents: an optical coherence tomography-based natural history study.

AIMS: To assess the fate of incomplete stent apposition (ISA) after deployment of sirolimus-eluting stents (SESs). METHODS AND RESULTS: Thirty-two patients having intravascular ultrasound (IVUS)-guided PCI with SESs underwent assessment of stent deployment with quantitative coronary angiography, IVUS, and optical coherence tomography (OCT) pre-procedure, post-procedure, and at 10 months follow-up. Incomplete stent apposition was defined as separation of a stent strut from the inner vessel wall by >160 microm. At follow-up, 4.67% of struts with ISA at deployment failed to heal and 7.59% which were well apposed did not develop neointimal hyperplasia even after 10 months. Lesion remodelling was responsible for the development of late ISA in only 0.37% of struts. Failure of adequate neointimal hyperplasia was quantitatively the most important mechanism responsible for persistent acute ISA, classified in previous studies, which relied only on follow-up OCT, as late ISA. Thrombus was visualized in 20.6% of struts with ISA at follow-up and in 2.0% of struts with a good apposition (P < 0.001). CONCLUSION: In patients with SESs, ISA can fail to heal and even complete apposition can be associated with no neointimal hyperplasia. Incomplete stent apposition without neointimal hyperplasia was significantly associated with the presence of OCT-detected thrombus at follow-up, and may constitute a potent substrate for late stent thrombosis.

Pentraxin 3 in unstable angina and non-ST-segment elevation myocardial infarction.

PURPOSE: We prospectively investigated the prognostic value of pentraxin 3 (PTX3) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: PTX3 may be a useful marker for localized vascular inflammation and damage to the cardiovascular system. Recent studies have shown that plasma PTX3 is elevated in patients with UA/NSTEMI; however, its prognostic value in UA/NSTEMI remains unclear. METHODS: PTX3, high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin I were measured on admission in 204 consecutive patients (mean age of 69 years; 144 males) hospitalized for UA/NSTEMI within 24h (mean of 7.5h) after the onset of chest symptoms. A cardiac event, which was defined as cardiac death, rehospitalization for acute coronary syndrome (ACS), or rehospitalization for worsening heart failure, was monitored for 6 months after admission. RESULTS: A total of 26 (13%) cardiac events occurred during the 6-month follow-up period. In a stepwise Cox regression analysis including 18 well-known clinical and biochemical predictors of ACS outcome, both PTX3 (relative risk 3.86 per 10-fold increment, P=0.01) and NT-proBNP (relative risk 2.16 per 10-fold increment, P=0.02), but not hsCRP, were independently associated with the 6-month cardiac event. The cardiac event rate was higher in patients with increased PTX3 (> or = 3.1ng/mL of median value) than those without (20% vs. 5.8%, P=0.003). A Kaplan-Meier analysis revealed that patients with increased PTX3 had a higher risk for cardiac events than those without (P=0.002). CONCLUSION: PTX3 and NT-proBNP may be potent and independent predictors for 6-month cardiac events in patients hospitalized for UA/NSTEMI within 24h after the onset. Measurement of plasma PTX3 may substantially improve the early risk stratification of patients with UA/NSTEMI.

Cystatin C in acute heart failure without advanced renal impairment.

BACKGROUND: The prognostic value of cystatin C relative to glomerular filtration rate (GFR) estimated by the Modification of Diet in Renal Disease Study (MDRD) equation modified for Japan has not been investigated in acute heart failure patients with normal to moderately impaired renal function. More accurate detection of mild renal impairment might improve the risk stratification of heart failure patients, especially patients with normal to moderately impaired renal function. METHODS: Cystatin C and creatinine levels were measured on admission in 328 consecutive patients hospitalized for worsening chronic heart failure with a GFR estimated by MDRD equation modified for Japan >or=30 mL/min/1.73 m(2). RESULTS: During a median follow-up period of 915 days, there were 52 (16%) cardiac deaths. In stepwise Cox regression analyses including cystatin C and GFR estimated by MDRD equation modified for Japan (either as continuous variables or as variables categorized into quartiles), cystatin C (P <.0001), but not GFR estimated by MDRD equation modified for Japan, was independently associated with cardiac mortality. Adjusted relative risk according to the quartiles of these markers and Kaplan-Meier analyses revealed that the cystatin C was a better marker to separate low-risk from high-risk patients. Furthermore, receiver-operating characteristic curve analyses of these markers revealed that cystatin C showed a higher precision in predicting cardiac mortality. CONCLUSION: Measurements of cystatin C might improve early risk stratification compared with GFR estimated by MDRD equation modified for Japan in acute heart failure patients with normal to moderately impaired renal function.

Restenosis and stent fracture following sirolimus-eluting stent (SES) implantation.

BACKGROUND: Restenosis still occurs, even with the sirolimus-eluting stent (SES), and the precise mechanisms and the impact of stent fracture on restensosis have not yet been elucidated. METHODS AND RESULTS: Intravascular ultrasound (IVUS)-guided SES implantation was performed in 184 lesions in 151 patients with stable and unstable angina. Serial (pre-, post- and follow-up) quantitative coronary angiography analysis was obtained in 169 lesions in 138 patients (angiographic follow-up rate: 91%) and 12-month clinical follow-up was done in all patients. Restenosis occurred in 13 (7.7%) of 169 lesions. Stent fracture occurred in 4 (2.4%) of 169 lesions at follow-up. Of the 13 restenotic lesions, 8 had intimal hyperplasia, 4 had stent fracture, and 1 had late stent thrombosis at 7 months. Although multivariate logistic regression analysis revealed that minimal lumen area (min-LA) post (p=0.027), total stent length (p=0.003) and diabetes (p=0.032) were significant independent predictors of restenosis, univariate analysis showed that stent fracture was more common in the restenosis than in the non-restenosis groups (p=0.001). CONCLUSIONS: Although min-LA post by IVUS, total stent length by QCA and diabetes are independent predictors for angiographic restenosis, stent fracture occurred in 4 lesions (2.4%) and all of them resulted in restenosis (31% of the restenosis). The impact of stent fracture and its potential role in the development of restenosis deserves further study.

Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes.

OBJECTIVES: To evaluate the feasibility of noninvasive assessment of the characteristics of disrupted atherosclerotic plaques, the authors interrogated the culprit lesions in acute coronary syndromes (ACS) by multislice computed tomography (CT). BACKGROUND: Disrupted atherosclerotic plaques responsible for ACS histopathologically demonstrate large lipid cores and positive vascular remodeling. It is expected that plaques vulnerable to rupture should bear similar imaging signatures by CT. METHODS: Either 0.5-mm x 16-slice or 64-slice CT was performed in 38 patients with ACS and compared with 33 patients with stable angina pectoris (SAP) before percutaneous coronary intervention. The coronary plaques in ACS and SAP were evaluated for the CT plaque characteristics, including vessel remodeling, consistency of noncalcified plaque (NCP <30 HU or 30 HU