Masanori Okumura

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.

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.

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.

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.

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.

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.

The Role of Multiple Imaging Modalities to Disclose the Mechanism of ACS Angioscopy in Comparison to Other Imaging Modalities Including OCT, IVUS and CTA

Aims: Whilst pathological and optical coherence tomography (OCT) studies have indicated that ACS lesions have either ruptured fibrous (RFC-ACS) or intact (IFC-ACS) fibrous caps, CT angiographic (CTA) characteristics of RFC-ACS include low-attenuation plaques and positive plaque remodelling. However, features associated with IFC-ACS have not been previously described. The aim of this study was to assess the CTA characteristics of IFC-ACS lesions.

IMPACT OF UNCOVERED STENT STRUTS ON OPTICAL COHERENCE TOMOGRAPHY (OCT) DETECTED THROMBUS FORMATION AT 10-MONTH FOLLOW-UP OF SIROLIMUS-ELUTING STENTS (SES)

Methods & Results: We performed 3993 strut analysis by OCT at every 1 millimeter in 30 patients with sirolimus-eluting stent (SES) at 10-month follow-up. Stent diameter used was 2.92+0.35mm with the length of 19.0+3.6mm. Of the 3993 struts, 622 (15.6%) struts remained uncovered (<10μm) and the remaining 3371 (84.4%) struts had covered strut (figure). While thrombi were identified as protruding masses, red thrombi were characterized as high-backscattering protrusions with signal-free shadowing and white thrombi were signal-rich and low-backscattering. Of the 25 thrombi, 3 were red, 8 white and 14 mixed thrombi. Of the 25 thrombi, 16 (64%) were observed on uncovered struts and the remaining 9 (36%) were seen on covered struts, with significantly higher incidence of thrombus on uncovered struts than on covered struts (p<0.001).