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. (Circulation. 2012;126:172-181.) Key Words: atherosclerosis Ⅲ endothelium Ⅲ natural history Ⅲ shear stress A therosclerosis is a systemic disease with focal and eccentric manifestations. 1 In a patient with coronary artery disease (CAD) and systemic risk factors, each coronary lesion progresses, regresses, or remains quiescent in an independent manner, 2 indicating that local vascular factors must be a major determinant responsible for the behavior of individual plaques. Editorial see p 161 Clinical Perspective on p 181The vascular endothelium is in a unique and pivotal position to respond to the extremely dynamic forces acting on the vessel wall because of the complex 3-dimensional (3D) Received January 27, 2012; accepted May 16, 2012. Identification of an early coronary atherosclerotic plaque likely to acquire high-risk characteristics and precipitate a new coronary event may allow for development of preemptive strategies to avert adverse events. The recent Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PR...

Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still technically challenging. The use of tapered-tip guidewires in these lesions may improve the success rate of PCI. In order to avoid the needless radiation exposure or contrast consumption, we have to determine a guideline for the termination of procedures in these lesions. We retrospectively analyzed the data of 182 patients between April 1997 and December 1999 (phase 1) and 80 patients between January and August 2001 (phase 2) who underwent angioplasty for CTO lesions ≥ 3 months. There were no significant differences in clinical or lesion characteristics except the use of tapered-tip guidewires. Tapered-tip guidewires were used in 60% of patients in phase 2 period but no patients in phase 1 period. The overall success rate of PCI was improved from 67% in phase 1 to 81% in phase 2 (P ‫؍‬ 0.019). In the phase 2 period, the success rate was higher in tapered-type occlusion (P ‫؍‬ 0.002) and shorter length of occlusion (P ‫؍‬ 0.004). Total procedure time was 46 ؎ 17 min and total volume of contrast dye was 180 ؎ 63 ml. The success rate was higher in patients treated by transradial coronary intervention (TRI) than transfemoral coronary intervention (89% vs. 64%; P ‫؍‬ 0.008). The use of tapered-tip guidewires can improve the success rate of PCI in CTO lesions. The following guideline for the termination of the procedures is reasonable: time from arterial access to successful penetration of a guidewire through occlusion ≤ 30 min; total procedure time ≤ 90 min; and total dye volume ≤ 300 ml. TRI can achieve a high success rate even in CTO lesions provided that the case selection is adequate. Cathet Cardiovasc Intervent 2003; 59:305-311.

BackgroundThe chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores.MethodsAn observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients’ reports, physicians’ records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed.ResultsThe CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients.ConclusionsSymptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized.Trial registrationClinical trial registered with UMIN (UMIN000003470).

Transradial coronary intervention (TRI) can be performed in elective patients with low incidence of access site complications. However, the feasibility of primary stent implantation by TRI is still not clear in patients with acute myocardial infarction (AMI). We prospectively randomized 149 patients out of 213 patients with AMI within 12 hr from onset into two groups: 77 patients treated by TRI (TRI group) and 72 patients by transfemoral coronary intervention (TFI; TFI group). We compared the incidences of major adverse cardiac events (MACE; repeat MI, target lesion revascularization, and cardiac death) during the initial hospitalization and 9-month follow-up periods in both groups. There were one patient who crossed over to the opposite arm, and two patients with severe bleeding complications in the TFI group. Background characteristics of patients were similar between the two groups. The success rate of reperfusion and the incidence of in-hospital MACE were similar in both groups (96.1% and 5.2% vs. 97.1% and 8.3% in TRI and TFI groups, respectively). In selected patients with AMI, primary stent implantation by TRI is feasible as compared to TFI.

A 6 Fr guiding catheter is commonly used in the percutaneous coronary intervention (PCI). However, one of the limitations of the 6 Fr guiding catheter is its weak backup support compared to a 7 or an 8 Fr guiding catheter. In this article, we present a new system for PCI called the five-in-six system. Between March 2003 and September 2003, this system was tried on eight chronic total occlusion cases. The advantage of the five-in-six system is that it increases backup support of a 6 Fr guiding catheter.

The molecular regulatory mechanisms and the characterization of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in hypoxia were studied in a mouse brain capillary endothelial cell line, MBEC4. Activation of GAPDH gene expression by hypoxia was suppressed by an intracellular Ca(2+) chelator and inhibited by a non-selective cation channel blocker or a Na(+)/Ca(2+) exchanger (NCX) blocker. Sequencing of reverse transcription-PCR products demonstrated that MBEC4 expressed an mRNA encoding NCX3, which functions even under cellular ATP-depleted conditions, in addition to mRNAs encoding NCX1 and NCX2. The inhibition of Ca(2+)/calmodulin-dependent protein kinases or c-Jun/AP-1 activation caused a significant decrease in the activation of GAPDH mRNA by hypoxia. These results suggest that hypoxia stimulates Ca(2+) influx through non-selective cation channels and causes the reverse operation of the three NCX isoforms, and consequently, increased intracellular Ca(2+) up-regulates GAPDH gene expression through an AP-1-dependent pathway. Furthermore, subcellular fractionation experiments showed that hypoxia increased GAPDH proteins not only in the cytosolic fraction, but also in the nuclear and particulate fractions, in which GAPDH should play no roles in glycolysis. However, the GAPDH activity did not rise in proportion to the increase of GAPDH protein by hypoxia even in the cytosolic fraction. These results suggest that not all hypoxia-induced GAPDH molecules contribute to glycolysis.

Besides lowering cholesterol, statins exert multiple effects, such as anti-inflammatory activity and improvement of endothelial cell function. We examined whether simvastatin (SS) protects against the development of elastase-induced pulmonary emphysema in mice by using mean linear intercepts of alveoli (Lm) as a morphometric parameter of emphysema. After injection of intratracheal elastase on day 0, C57BL/6 mice were treated daily with SS (SS+ group) or PBS (SS− group) for 2 wk. A 21% decrease in Lm on day 7 was observed in the SS+ group vs. the SS− group. Anti-inflammatory effects of SS were observed as a decrease in percentage of neutrophils up to day 3, and in hydroxyproline concentration on day 3, in bronchoalveolar lavage fluid (BALF). SS also increased the number of proliferating cell nuclear antigen (PCNA)-positive alveolar epithelial cells between days 3 and 14. To confirm the role of statins in promoting proliferation of alveolar cells, mice were treated with SS (SS+) vs. PBS (SS−) for 12 days, starting 3 wk after elastase administration. After SS treatment, Lm decreased by 52% and PCNA-positive alveolar epithelial cells increased compared with the SS− group. Concentrations of vascular endothelial growth factor in BALF and endothelial nitric oxide synthase protein expression in pulmonary vessels tended to be higher in the SS+ group vs. the SS− group in this protocol. In conclusion, SS inhibited the development of elastase-induced pulmonary emphysema in mice. This therapeutic effect was due not only to anti-inflammation but also to the promotion of alveolar epithelial cell regeneration, partly mediated by restoring endothelial cell functions.

This study confirmed the complex pathophysiology of COPD-related osteoporosis, including the influence of gender, clinical phenotype and genetic factors.