Sunao Nakamura

Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Plaque Characteristics: The PREDICTION Study

Background— Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events. Methods and Results— Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo. Three-vessel vascular profiling (2.7 arteries per patient) was performed at baseline in 506 patients with an acute coronary syndrome treated with a percutaneous coronary intervention and in a subset of 374 (74%) consecutive patients 6 to 10 months later to assess plaque natural history. Each reconstructed artery was divided into sequential 3-mm segments for serial analysis. One-year clinical follow-up was completed in 99.2%. Symptomatic clinical events were infrequent: only 1 (0.2%) cardiac death; 4 (0.8%) patients with new acute coronary syndrome in nonstented segments; and 15 (3.0%) patients hospitalized for stable angina. Increase in plaque area (primary end point) was predicted by baseline large plaque burden; decrease in lumen area (secondary end point) was independently predicted by baseline large plaque burden and low endothelial shear stress. Large plaque size and low endothelial shear stress independently predicted the exploratory end points of increased plaque burden and worsening of clinically relevant luminal obstructions treated with a percutaneous coronary intervention at follow-up. The combination of independent baseline predictors had a 41% positive and 92% negative predictive value to predict progression of an obstruction treated with a percutaneous coronary intervention. Conclusions— Large plaque burden and low local endothelial shear stress provide independent and additive prediction to identify plaques that develop progressive enlargement and lumen narrowing. Clinical Trial Registration— URL: http:www.//clinicaltrials.gov. Unique Identifier: NCT01316159.

A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan

AIMS Theoretically, bioresorbable vascular scaffolds (BVSs) may provide superior long-term results compared with permanent metallic drug-eluting stents (DESs). However, whether BVSs are as safe and effective as metallic DESs prior to complete bioresorption is unknown. METHODS AND RESULTS ABSORB Japan was a single-blind, multicentre, active-controlled, randomized trial designed to support regulatory approval of the Absorb BVS in Japan. Eligible patients with one or two de novo lesions in different epicardial vessels were randomized at 38 Japanese sites in a 2:1 ratio to Absorb BVS vs. cobalt-chromium everolimus-eluting stents (CoCr-EESs). The primary endpoint was target lesion failure [TLF: a composite of cardiac death, myocardial infarction attributable to target vessel, or ischaemia-driven target lesion revascularization (ID-TLR)] at 12 months, powered for non-inferiority. The major secondary endpoint was angiographic in-segment late lumen loss (LLL) at 13 months. A total of 400 patients were randomized to BVSs (266 patients and 275 lesions) or CoCr-EESs (134 patients and 137 lesions). TLF through 12 months was 4.2% with BVSs and 3.8% with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.39% (3.95%); Pnon-inferiority < 0.0001]. Definite/probable stent/scaffold thrombosis at 12 months occurred in 1.5% of the patients with both devices (P = 1.0), and ID-TLR for restenosis was infrequent (1.1% with BVSs and 1.5% with CoCr-EESs, P = 1.0). With 96.0% angiographic follow-up, in-segment LLL at 13 months was 0.13 ± 0.30 mm with BVSs and 0.12 ± 0.32 mm with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.01 (0.07); Pnon-inferiority < 0.0001). CONCLUSION In the ABSORB Japan randomized trial, 12-month clinical and 13-month angiographic outcomes of BVSs were comparable to CoCr-EESs. CLINICAL REGISTRATION ClinicalTrials.gov, number NCT01844284.

Primary stent implantation is superior to balloon angioplasty in acute myocardial infarction: Final results of the primary angioplasty versus stent implantation in acute myocardial infarction (PASTA) trial

Several studies have shown that stent implantations in acute myocardial infarction (AMI) result in better short‐ and long‐term outcomes than primary balloon angioplasty. These results, however, have not been ascertained in randomized trials. We randomized 136 patients out of 208 patients with AMI within 12 hr from onset into two groups: 69 patients with primary balloon angioplasty (POBA group) and 67 patients with primary stent implantation (STENT group). We compared the incidences of major cardiac events (repeat MI, target lesion revascularization, and cardiac death) and angiographic parameters during hospitalization and follow‐up periods up to 12 months in these two groups. There was no significant difference in the reperfusion success rates. The incidences of major cardiac events were lower in the STENT group than in the POBA group during hospitalization, the first 6 months and 12 months (6% vs. 19%, P = 0.023; 21% vs. 46%, P < 0.0001; 22% vs. 49%, P = 0.0011). Minimum lumen diameters were significantly bigger in the STENT group than the POBA group at predischarge angiogram and 6‐month follow‐up (2.85 ± 0.62 vs. 2.08 ± 0.82 mm, P < 0.0001; 2.24 ± 0.64 vs. 1.72 ± 0.76, P = 0.002). Restenosis rates at 6‐month follow‐up were significantly lower in the STENT group than in the POBA group (17% vs. 37.5%, P = 0.02). In selected patients with AMI, primary stent implantation results in a lower incidence of major cardiac events during the first 12 months, postprocedure, and less frequent 6‐month restenosis than primary balloon angioplasty. Cathet. Cardiovasc. Intervent. 48:262–268, 1999.

Optical coherence tomography versus intravascular ultrasound to evaluate coronary artery disease and percutaneous coronary intervention.

OBJECTIVES We compared intravascular ultrasound (IVUS) and 2 different generations of optical coherence tomography (OCT)-time-domain OCT (TD-OCT) and frequency-domain OCT (FD-OCT)-for the assessment of coronary disease and percutaneous coronary intervention (PCI) using stents. BACKGROUND OCT is a promising light-based intravascular imaging modality with higher resolution than IVUS. However, the paucity of data on OCT image quantification has limited its application in clinical practice. METHODS A total of 227 matched OCT and IVUS pull backs were studied. One hundred FD-OCT and IVUS pull backs in nonstented (n = 56) and stented (n = 44) vessels were compared. Additionally, 127 matched TD-OCT and IVUS images were compared in stented vessels. RESULTS FD-OCT depicted more severe native coronary disease than IVUS; minimal lumen area (MLA) was 2.33 ± 1.56 mm(2) versus 3.32 ± 1.92 mm(2), respectively (p < 0.001). Reference vessel dimensions were equivalent between FD-OCT and IVUS in both native and stented coronaries, but TD-OCT detected smaller reference lumen size compared with IVUS. Immediately post-PCI, in-stent MLAs were similar between FD-OCT and IVUS, but at follow-up, both FD-OCT and TD-OCT detected smaller MLAs than did IVUS, likely due to better detection of neointimal hyperplasia (NIH). Post-PCI malapposition and tissue prolapse were more frequently identified by FD-OCT. CONCLUSIONS FD-OCT generates similar reference lumen dimensions but higher degrees of disease severity and NIH, as well as better detection of malapposition and tissue prolapse compared with IVUS. First-generation TD-OCT was associated with smaller reference vessel dimensions compared with IVUS.

Frequency-domain optical coherence tomography assessment of unprotected left main coronary artery disease-a comparison with intravascular ultrasound.

To investigate safety and feasibility of imaging unprotected left main (ULM) using frequency‐domain optical coherence tomography (FD‐OCT) compared with intravascular ultrasound (IVUS).

Determination of cut-off levels for on-clopidogrel platelet aggregation based on functional CYP2C19 gene variants in patients undergoing elective percutaneous coronary intervention

INTRODUCTION Carriers of reduced-function CYP2C19 allele on antiplatelet therapy show diminished platelet inhibition and higher rate of clinical risk. The purpose of this study was to determine cut-off levels of VerifyNow P2Y12 system associated with effective inhibition of on-clopidogrel platelet aggregation to predict carriers of CYP2C19 reduced-function allele among patients undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS We enrolled 202 consecutive patients with stable coronary artery disease (CAD) undergoing PCI and treated with clopidogrel. All patients underwent CYP2C19 genotyping and measurement of residual platelet aggregation by VerifyNow system. RESULTS Carriers of CYP2C19 reduced-function allele constituted 131 (65%) of 202 CAD patients. Platelet inhibition measured by P2Y12 reaction units (PRU) and %inhibition was diminished in carriers compared with noncarriers (PRU: 290.0±81.2 vs 217.6±82.4, p<0.001, %inhibition: 17.9±17.8 vs 35.5±22.8, p<0.001, respectively). Multiple logistic regression analysis identified PRU and %inhibition as significant predictors of carrier state [odds ratio (OR) 4.95; 95% confidence interval (95%CI): 2.49 to 9.85; p<0.001, OR 5.55; 95%CI: 2.80 to 10.99; p<0.001, respectively]. Receiver-operating characteristic analysis showed that PRU and %inhibition were significant predictors of carrier state [area under the curve (AUC) 0.736 (95%CI: 0.664 to 0.808; p<0.001), AUC 0.727 (95%CI: 0.651 to 0.803; p<0.001), respectively]. The cut-off levels of PRU and %inhibition were 256 and 26.5% for the identification of carriers. CONCLUSIONS Our results suggested that the cut-off levels of PRU and %inhibition to discriminate carriers of CYP2C19 reduced-function allele from noncarriers are potentially useful clinically to provide optimal clopidogrel therapy in patients with stable CAD undergoing PCI.

Coronary plaque component in patients with vasospastic angina: A virtual histology intravascular ultrasound study

BACKGROUND Coronary spasm plays an important role in the pathogenesis of ischemic heart disease. However, tissue components of coronary plaque in patients with vasospastic angina (VSA) have been unknown. This study used virtual histology (VH)-intravascular ultrasound (IVUS) to elucidate the tissue component of spastic coronary arteries and its gender differences in patients with VSA. METHODS According to acetylcholine provocation tests, the study subjects (42 patients [19 men, 23 women, 61 ± 13 years]) were divided into 2 groups: the VSA group of 26 patients and the non-VSA group of 16 patients. After nitrate injection, IVUS volumetric analysis was done, and the parameters were compared between the groups. RESULTS Although clinical demographics were almost identical between the groups, VSA group had lower plasma adiponectin level (5.9 ± 3.3 μg/ml vs. 11.2 ± 7.6 μg/ml, p=0.007) and tended to have higher high-sensitivity C-reactive protein (0.15 ± 0.24 mg/dl vs. 0.06 ± 0.04 mg/dl, p=0.1) than non-VSA group. VSA group had diffusely thickened intima (% plaque volume, 34 ± 11% vs. 27 ± 7%, p=0.01) compared with non-VSA group. However, plaque components of patients with VSA were similar with that of non-VSA patients (dense calcium, 4 ± 6% vs. 3 ± 4%; necrotic core, 10 ± 9% vs. 8 ± 6%; fibrofatty, 19 ± 16% vs. 22 ± 11%; and fibrous, 67 ± 16% vs. 67 ± 9%). Although male patients with VSA had atherogenic lipid and metabolic profiles than female VSA patients, there were no significant gender differences in the volumetric IVUS parameters and plaque components. CONCLUSIONS Compared with non-VSA patients, VSA patients had diffusely thickened fibrous-dominant coronary plaque without gender difference, and that might suggest the role of vasospasm in the development of atherosclerosis.

Clinical and Procedural Predictors of Suboptimal Outcome After the Treatment of Drug-Eluting Stent Restenosis in the Unprotected Distal Left Main Stem The Milan and New-Tokyo (MITO) Registry

Background— Few data are available regarding the optimal revascularization strategy for unprotected distal left main coronary artery (UDLM) in-stent restenosis (ISR). Methods and Results— Between April 2002 and December 2008, UDLM-ISR following drug-eluting stent (DES) implantation occurred in 92 of 474 patients (19.4%). Of these, 8 (8.7%) who underwent a coronary artery bypass graft (CABG) were excluded, and the remaining 84 (91.3%) who underwent percutaneous coronary intervention (PCI) (43 plain old balloon angioplasty [POBA] and 41 DES) were analyzed to assess the feasibility of PCI for UDLM-ISR. The overall cardiac death, myocardial infarction (MI), and major adverse cardiac events during the follow-up period (median, 24 months) occurred in 4, 2, and 31 patients, respectively. Repeat target lesion revascularization (TLR) occurred in 28 patients. The incidence of repeat TLR was higher following PCI with POBA than with DES (hazard ratio [HR], 2.79; 95% CI, 1.23–6.34; P=0.014). On Cox regression analysis, the independent predictors of repeat TLR were treatment with POBA (HR, 3.29; 95% CI, 1.41–7.69; P=0.006) and EuroSCORE (European System for Cardiac Operative Risk Evaluation) >6 (HR, 2.53; 95% CI, 1.02–6.28; P=0.045). More complex lesions requiring a 2-stent strategy were associated with a higher occurrence of TLR for restenosis of the left circumflex coronary artery ostium (LCX-ISR) (HR, 2.51; 95% CI, 1.59–3.97; P=0.001) as well as repeat TLR for recurrent LCX-ISR (HR, 4.32; 95% CI, 0.97–19.20; P=0.05) compared to a 1-stent strategy. No cardiac death at 2 years occurred in patients with LCX-ISR. Conclusions— UDLM restenosis is better treated with DES than with POBA. The rate of recurrent ISR following repeat PCI was high, whereas the rates of MI and death were relatively low. Complex lesions requiring a 2-stent strategy had a higher recurrence rate at the ostial LCX but without an associated increased risk of MI and death.

The STENTYS® paclitaxel-eluting stent in the treatment of unprotected distal left main

Vessel tapering represents an important limitation of the balloon‐expandable drug‐eluting stent (DES) in the treatment of distal unprotected left main coronary artery (ULMCA) lesions. In this study, we assessed the suitability of the STENTYS DES(P), a self‐apposing nitinol paclitaxel‐eluting stent, for use in the treatment of distal ULMCA lesions.

Impact of residual chronic total occlusion of right coronary artery on the long-term outcome in patients treated for unprotected left main disease: the Milan and New-Tokyo registry.

Background—The presence of chronic total occlusion of the right coronary artery (CTO-RCA) in patients undergoing percutaneous interventions for unprotected left main (ULM) disease may affect the prognosis. In this study, we evaluated the immediate results and follow-up of patients with ULM-percutaneous interventions and with or without associated CTO-RCA. Methods and Results—Between March 2002 and December 2008, a total of 568 consecutive patients with ULM stenosis treated with drug-eluting stent were included in this analysis. The mean EuroScore and SYNTAX scores were 4.05±2.62 and 28.12±10.82, respectively. Of these, 522 had ULM lesions without residual CTO-RCA (493 ULM without CTO-RCA+29 ULM with treated CTO-RCA), and 46 patients had residual CTO-RCA. At 1466 days (interquartile range, 1150–1917) follow-up, the cardiac-death occurred in 41 patients (7.2%). Cardiac-death was more frequently observed in patients with ULM and residual CTO-RCA as compared with those without residual CTO-RCA (adjusted hazard ratios, 2.163 [95% confidence interval, 1.018–4.597]; P=0.045). However, target lesion revascularization occurred less frequently in patients with residual CTO-RCA (adjusted hazard ratios, 0.321 [95% confidence interval, 0.13–0.794]; P=0.014), resulting in the similar major adverse cardiovascular events rates between the 2 groups. When we analyzed patients with concomitant ULM and CTO-RCA, cardiac-death was significantly higher in patients with residual as compared with treated CTO-RCA (log-rank P=0.01) despite no difference in baseline characteristics. Conclusions—Cardiac-death occurred more frequently in patients with residual CTO-RCA as compared with those without residual CTO-RCA. These findings suggest that recanalization of CTO-RCA has significant impact on the long-term cardiac-mortality in patients undergoing ULM-percutaneous interventions probably by offering reserve coronary circulation, if in-stent restenosis were to occur in the treated left main.