Keiko Asakura

Retrograde Percutaneous Recanalization of Chronic Total Occlusion of the Coronary Arteries Procedural Outcomes and Predictors of Success in Contemporary Practice

Background— Retrograde approach through collaterals has been introduced for percutaneous recanalization of chronic total occlusion (CTO) of the coronary arteries. We investigated the safety and efficacy of retrograde approaches used for percutaneous recanalization of CTO in a consecutive series of patients. Methods and Results— We studied 157 consecutive patients who underwent retrograde CTO recanalization between 2003 and 2008 at a single center. A total of 118 (75.2%) of these patients have had previously failed antegrade attempts. Septal, epicardial, and saphenous vein graft collaterals were used in 67.5%, 24.8%, and 7.6% of cases, respectively. Collateral channel was crossed by guide wire successfully in 115 (73.2%) cases, and the procedure was successful by retrograde approach in 103 (65.6%) cases. Collateral channels (CCs) were graded as follows: CC0, no continuous connection; CC1, continuous thread-like connection; and CC2, continuous, small sidebranch-like connection. CC1, collateral tortuosity 90° ( P =0.0007), and nonvisibility of connection with recipient vessel were found to be significant predictors of procedural failure. The CC dissection was observed in 6 patients, with 1 needing coil embolization and others who were managed conservatively. The major adverse cardiac events were low, with 1 coronary artery bypass graft, 1 Q-wave myocardial infarction, 5 non–Q-wave myocardial infarctions, and no deaths in this group of patients. Conclusions— The retrograde approach in CTO percutaneous coronary intervention is effective in recanalizing CTO. The success rate by retrograde approach was 65.6%, and final success was 85% in this group with acceptable overall adverse events. We have identified predictors of failure related to collateral morphology. Received November 28, 2008; accepted February 13, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Retrograde approach through collaterals has been introduced for percutaneous recanalization of chronic total occlusion (CTO) of the coronary arteries. We investigated the safety and efficacy of retrograde approaches used for percutaneous recanalization of CTO in a consecutive series of patients. Methods and Results—We studied 157 consecutive patients who underwent retrograde CTO recanalization between 2003 and 2008 at a single center. A total of 118 (75.2%) of these patients have had previously failed antegrade attempts. Septal, epicardial, and saphenous vein graft collaterals were used in 67.5%, 24.8%, and 7.6% of cases, respectively. Collateral channel was crossed by guide wire successfully in 115 (73.2%) cases, and the procedure was successful by retrograde approach in 103 (65.6%) cases. Collateral channels (CCs) were graded as follows: CC0, no continuous connection; CC1, continuous thread-like connection; and CC2, continuous, small sidebranch-like connection. CC1, collateral tortuosity <90°, and angle with recipient vessel <90° (P<0.0001) were significant predictors of success. Epicardial channel use (P=0.01), CC0, corkscrew channel (P<0.0001), angle with recipient vessel >90° (P=0.0007), and nonvisibility of connection with recipient vessel were found to be significant predictors of procedural failure. The CC dissection was observed in 6 patients, with 1 needing coil embolization and others who were managed conservatively. The major adverse cardiac events were low, with 1 coronary artery bypass graft, 1 Q-wave myocardial infarction, 5 non–Q-wave myocardial infarctions, and no deaths in this group of patients. Conclusions—The retrograde approach in CTO percutaneous coronary intervention is effective in recanalizing CTO. The success rate by retrograde approach was 65.6%, and final success was 85% in this group with acceptable overall adverse events. We have identified predictors of failure related to collateral morphology.

Prevalence of ulcerative colitis and Crohn’s disease in Japan

PurposeThe prevalence of inflammatory bowel diseases is much lower in Asian countries, including Japan, than in Western countries, but it is rapidly increasing. However, no recent reports describe the current prevalence of these diseases in Japan, so we performed a descriptive epidemiological study to remedy this situation and to elucidate various characteristics of inflammatory bowel diseases in this country.MethodsJapan has a nationwide registration system of patients with intractable diseases, including ulcerative colitis and Crohn’s disease. To calculate the age-standardized prevalence, we used this registration system to collect patient data, and we obtained detailed population data from the Japanese government’s population estimates made in 2003 and 2004 and from the 2005 population census. In addition, information about the characteristics of ulcerative colitis and Crohn’s disease patients was collected through the registration system.ResultsThe age-standardized prevalence of ulcerative colitis in Japan in 2005 was 63.6 per 100,000 persons, and that of Crohn’s disease was 21.2. Patient numbers have been steadily increasing with time. The age distribution was found to differ between the two diseases, with Crohn’s disease affecting mainly younger people. In both diseases, more than 50% of the patients were male, and over 80% of the patients were classified as mild to moderate in terms of severity.ConclusionsThe prevalence of inflammatory bowel diseases in Japan is still much lower than in Western countries. Surveillance should be continued, and research to clarify their etiologies in association with the increasing number of patients in Japan is needed.

The efficacy of a bilateral approach for treating lesions with chronic total occlusions the CART (controlled antegrade and retrograde subintimal tracking) registry.

OBJECTIVES The aim of this study was to evaluate the safety and feasibility of a new concept for chronic total occlusion (CTO) recanalization-using a bilateral approach that utilizes a Controlled Antegrade and Retrograde subintimal Tracking (CART) technique. BACKGROUND Successful percutaneous recanalization of coronary CTOs results in improved long-term outcomes. The recanalization of CTOs in native coronary arteries no doubt represents one of the most technically challenging of interventional procedures. METHODS A total of 224 consecutive patients (mean age 61 +/- 9 years; 86.2% men) were enrolled in this prospective multicenter registry. This technique combines the simultaneous use of antegrade and retrograde approaches. A subintimal dissection is created in both antegrade and retrograde fashion, thereby limiting the extension of the subintimal dissection within the CTO portion. RESULTS Of 224 CTO lesions (>3 months in duration) undergoing attempted recanalization using the CART technique, 145 cases (64.7%) had undergone previous CTO recanalization attempts. The success rates of crossing in a retrograde fashion with a wire and a balloon were 87.9% and 79.9%, respectively. The overall technical and procedural success rates achieved in this registry were 92.4% and 90.6%, respectively. CONCLUSIONS A bilateral approach for CTO lesions using the CART technique is feasible, safe, and has a higher success rate than previous approaches. These results indicate that a bilateral technique can solve a major dilemma that commonly affects CTO procedures.

Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound.

OBJECTIVES The aim of this study was to evaluate the effect of treatment with statins on the progression of coronary atherosclerotic plaques of a nonculprit vessel by serial volumetric virtual histology (VH) intravascular ultrasound (IVUS). BACKGROUND Recent clinical trials have demonstrated a reduction of atherosclerotic plaque, yet whether statin therapy affects the change in components of plaque remains unknown. METHODS This study was a nonrandomized and nonblinded design. Eighty patients with stable angina pectoris were divided into either the fluvastatin group (n = 40) or the control group (n = 40) according to their total or low-density lipoprotein (LDL) cholesterol level. The volume of each plaque component (dense calcium, fibrous tissue, fibro-fatty, or necrotic core) was evaluated at baseline and at 12-month follow-up. RESULTS The LDL cholesterol and high-sensitivity C-reactive protein (hsCRP) levels in the fluvastatin group were significantly decreased at time of follow-up. In VH IVUS findings, fibro-fatty volume was significantly decreased (baseline 80.1 +/- 57.9 mm(3) vs. follow-up 32.5 +/- 27.7 mm(3), p < 0.0001) and fibrous tissue volume was increased (baseline 146.5 +/- 85.6 mm(3) vs. follow-up 163.3 +/- 94.5 mm(3), p < 0.0001) in the fluvastatin group. In the control group, the volumes of all plaque components without fibrous tissue were significantly increased. Change in fibro-fatty volume has a significant correlation with a change in LDL cholesterol level (R = 0.703, p < 0.0001) and change in hsCRP level (R = 0.357, p = 0.006). CONCLUSIONS One-year lipid-lowering therapy by fluvastatin showed significant regression of plaque volume and alterations in atherosclerotic plaque composition with a significant reduction of fibro-fatty volume.

Plaque characterisation by Virtual Histology intravascular ultrasound analysis in patients with type 2 diabetes

Objectives: To evaluate the in-vivo plaque composition and characteristics in patients with type 2 diabetes mellitus (DM) using Virtual Histology intravascular ultrasound (VH IVUS). Methods: In 90 patients with stable angina pectoris, de novo target vessels were studied and plaque components were analysed. Patients were divided into two groups: a diabetic group (36 vessels) and a non-diabetic group (54 vessels). Results: The percentage area of necrotic core and dense calcium were significantly larger in the DM group than the non-DM group (necrotic core: 11.0% (interquartile range (IQR): 7.2–15.2%) vs 7.6% (IQR 5.6–13.2%), p = 0.03; dense calcium: 5.6% (IQR: 2.3–7.3%) vs 2.9% (IQR: 1.7–4.9%), p = 0.01). The DM group presented with a significantly higher presence of at least one VH IVUS-derived thin-cap fibroatheroma (VHD-TCFA) (75% vs 41%, p = 0.001) and VH IVUS-derived fibrocalcific atheroma (VHD-FCA) (75% vs 40%, p = 0.001). In the DM group, 53% of the vessels had both VHD-TCFA and VHD-FCA, which was significantly higher than non-DM group (17%, p = 0.0004). Conclusions: Coronary plaque characteristics in DM patients showed an increased amount of dense calcium and necrotic core, as well as a higher frequency of VHD-TCFA and VHD-FCA. Atherosclerosis of the target vessel was more advanced in diabetic patients.

Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor

Emodin is an active component of a traditional Chinese and Japanese medicine isolated from the root and rhizomes of Rheum palmatum L. Here, we show that emodin significantly induces cytotoxicity in the human myeloma cells through the elimination of myeloid cell leukemia 1 (Mcl-1). Emodin inhibited interleukin-6–induced activation of Janus-activated kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3), followed by the decreased expression of Mcl-1. Activation of caspase-3 and caspase-9 was triggered by emodin, but the expression of other antiapoptotic Bcl-2 family members, except Mcl-1, did not change in the presence of emodin. To clarify the importance of Mcl-1 in emodin-induced apoptosis, the Mcl-1 expression vector was introduced into the human myeloma cells by electroporation. Induction of apoptosis by emodin was almost abrogated in Mcl-1–overexpressing myeloma cells as the same level as in parental cells, which were not treated with emodin. In conclusion, emodin inhibits interleukin-6–induced JAK2/STAT3 pathway selectively and induces apoptosis in myeloma cells via down-regulation of Mcl-1, which is a good target for treating myeloma. Taken together, our results show emodin as a new potent anticancer agent for the treatment of multiple myeloma patients. [Mol Cancer Ther 2007;6(3):987–94]

Predictors of angiographic restenosis after drug eluting stents in the coronary arteries: contemporary practice in real world patients

AIMS Drug eluting stents (DES) have been used routinely in a wide variety of clinical situations. The impact of DES on reducing restenosis has not been uniform across complex subsets and limited data is available examining predictors of restenosis in unselected population. METHODS AND RESULTS We investigated predictors of angiographic restenosis in an unselected population. The study population consisted of 4,143 lesions and angiographic follow-up was available for 3,020 (73%) lesions in 1,885 patients. The intravascular ultrasound (IVUS) was used in 95% of the patients during the procedure. Angiographic restenosis was seen in 339 (11.2%) lesions and target lesion revascularisation was performed in 290 (9.6%) lesions. The patient population included large numbers of renal failure patients on haemodialysis, ISR, and Type C lesions with routine use of intravascular ultrasound. We identified diabetes mellitus, renal failure, Type C lesions, calcified lesion, tortuous lesion, ISR, long lesion, small baseline diameter and final vessel diameter as predictors of restenosis. On multivariate analysis diabetes (OR 1.45, 95% CI 1.07-1.97, p= 0.01), renal failure on haemodialysis (OR 2.02, 95% CI 1.37-3.27, p=0.001), ISR (OR 3.56, 95% CI 2.16-5.89, P<0.001), lesion length (OR 1.02, CI 1.01-1.03.P<0.001), reference vessel diameter (OR 0.50, 95% CI 0.31-0.80, p=0.005) and post-intervention IVUS lumen area (p<0.001) were independent predictors of angiographic restenosis. Female gender (OR 0.61, 95% CI 0.410.91, p=0.015) was found to have a negative correlation for ISR. We did not find any significant difference in restenosis between the usage of sirolimus and paclitaxel eluting stents. CONCLUSIONS DES usage was associated with overall low in-stent restenosis and we have identified several clinical, angiographic, and IVUS predictors of angiographic restenosis in unselected patients with complex anatomy.

Impact of Frequency-Domain Optical Coherence Tomography Guidance for Optimal Coronary Stent Implantation in Comparison With Intravascular Ultrasound Guidance

Background— Frequency-domain optical coherence tomography (FD-OCT) is a novel, high resolution intravascular imaging modality. Intravascular ultrasound (IVUS) is a widely used conventional imaging modality for achieving optimal stent deployment. The aim of this study was to evaluate the impact of FD-OCT guidance for coronary stent implantation compared with IVUS guidance. Methods and Results— A total of 70 patients with de novo coronary artery lesions and either unstable or stable angina pectoris were enrolled in this randomized study (optical coherence tomography [OCT] group: n=35, IVUS group: n=35). In the OCT group, stent implantation was performed under FD-OCT guidance alone and final stent expansion was evaluated by IVUS. In the IVUS group, conventional IVUS guidance was used and final stent apposition was evaluated by FD-OCT. There were no significant differences regarding the procedural, fluoroscopy time, and contrast volume. Although device and clinical success rates also were similar, the visibility of vessel border was significantly lower in the OCT group (P<0.05). Minimum and mean stent area and focal and diffuse stent expansion were smaller (6.1±2.2 mm versus 7.1±2.1 mm, 7.5±2.5 versus 8.7±2.4 mm, 64.7±13.7% versus 80.3±13.4%, 84.2±15.8% versus 98.8±16.5%, P<0.05, respectively), and the frequency of significant residual reference segment stenosis at the proximal edge was higher in the OCT group (P<0.05). Incomplete apposed struts in both groups were similar (P=0.34). Conclusions— FD-OCT guidance for stent implantation was associated with smaller stent expansion and more frequent significant residual reference segment stenosis compared with conventional IVUS guidance.

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence

Background:Multiple early gastric cancers (EGCs) may develop in 6–14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence.Methods:Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed.Results:The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71–83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30–18.8).Conclusion:CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

A comparison of clinical presentations, angiographic patterns and outcomes of in-stent restenosis between bare metal stents and drug eluting stents

AIMS This paper studies in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) following bare-metal stent (BMS) and drug-eluting stent (DES) in all consecutive patients between 2004 and 2007 undergoing PCI for ISR lesions at our centre. METHODS AND RESULTS We compared the clinical presentation, pattern and angiographic outcomes in 838 patients with BMS ISR (487) and SES ISR (351). About 18% of the patients presented with acute coronary syndrome with 2% presenting as ST elevation myocardial infarction, similar in both groups. Angiographic pattern was predominantly focal with SES ISR (47%SES ISR vs. 19% BMS ISR; p<0.001) and diffuse with BMS ISR (SES ISR 16% vs. BMS ISR 36%; p=0.003). In our series the use of balloon angioplasty was higher for the treatment of SES ISR patients as compared to BMS ISR (41.6% vs. 18.3%; p<0.001) and the usage of stent was higher in BMS ISR patients (38.6% vs. 23.4%; p<0.001). Angiographic recurrent restenosis with conventional treatment in a consecutive series of patients was 38.6% and target lesion revascularisation was seen in 33.6%. These outcomes were seen slightly higher in SES ISR group (41.1% vs. 36.9%, p=ns). We have identified unstable angina at presentation (OR 3.02; 95%CI: 1.58-5.77, p=0.001), focal pattern of ISR (OR 0.50; 95% CI: .25-.99, p=0.04), stent usage (OR .25; 95% CI .13-.47, p<0.001), and baseline% diameter stenosis (OR1.03; 95%CI: 1.03-1.06, p=0.01) as independent predictors of BMS ISR recurrent restenosis. Unstable angina, focal pattern of ISR, reference vessel diameter, and% diameter stenosis were shown to be independent predictors of SES ISR. CONCLUSIONS ISR is not a benign condition, and one fifth of the patients presented with acute coronary syndrome. The pattern of restenosis is predominantly non-focal with BMS ISR and focal with SES ISR. Recurrent restenosis rates are high following conventional treatment and further optimal therapies mainly with SES ISR needs to defined.