Taketsugu Tsuchiya

Endovascular Treatment for Infrainguinal Vessels in Patients With Critical Limb Ischemia OLIVE Registry, a Prospective, Multicenter Study in Japan With 12-Month Follow-up

Background—Recent technical advances have made endovascular treatment (EVT) an alternative first-line treatment for critical limb ischemia. Methods and Results—A prospective multicenter study was conducted to evaluate the clinical outcomes of 314 Japanese critical limb ischemia patients (mean age, 73±10 years) with infrainguinal arterial lesions who underwent EVT. Patients were enrolled from December 2009 to July 2011 and were followed-up for 12 months. The primary end point was amputation-free survival (AFS) at 12 months. Secondary end points were anatomic, clinical, and hemodynamic measures, including 12-month freedom from major adverse limb events. The 12-month AFS rate was 74%, with body mass index <18.5 (hazard ratio [HR], 2.22; P=0.008), heart failure (HR, 1.73; P=0.04), and wound infection (HR, 1.89; P=0.03) associated with a poor prognosis for AFS. The 12-month major adverse limb event-free rate was 88%, with hemodialysis (HR, 1.98; P=0.005), heart failure (HR, 1.69; P=0.02), and Rutherford classification 6 (HR, 2.25; P=0.002) associated with a poor prognosis for major adverse limb events. The median time for wound healing was 97 days, with body mass index <18.5 (HR, 0.54; P=0.03) and wound infection (HR, 0.60; P=0.04) being significant risk factors for unhealed wounds after EVT. At 12 months, 34% had undergone reintervention (bypass surgery, 2.6%; repeat EVT, 31.7%), and 73% were major adverse event–free. Conclusions—The high reintervention rate notwithstanding, EVT was an effective treatment for Japanese critical limb ischemia patients with infrainguinal disease, with satisfactory AFS and major adverse limb event-free rates. The results of this study will be helpful for the future evaluation of critical limb ischemia therapy. Clinical Trial Registration—URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000002830.

Cilostazol Reduces Angiographic Restenosis After Endovascular Therapy for Femoropopliteal Lesions in the Sufficient Treatment of Peripheral Intervention by Cilostazol Study

Background— It remains unclear whether cilostazol, which has been shown to improve the clinical outcomes of endovascular therapy for femoropopliteal lesions, also reduces angiographic restenosis. Methods and Results— The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study investigated whether cilostazol reduces the 12-month angiographic restenosis rate after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Two hundred patients with femoropopliteal lesions treated from March 2009 to April 2011 at 13 cardiovascular centers were randomly assigned 1:1 to receive oral aspirin with or without cilostazol. The primary end point was 12-month angiographic restenosis rate. Secondary end points were the restenosis rate on duplex ultrasound, the rate of major adverse cardiac events, and target lesion event-free survival. Researchers evaluated all follow-up data and assessed the end points in a blinded fashion. The mean lesion length and reference vessel diameter at the treated segment were 128±86 mm and 5.4±1.4 mm, respectively. The frequency of stent used was similar between groups (88% versus 90% in the cilostazol and noncilostazol group, respectively, P=0.82). During the 12-month follow-up period, 11 patients died and 152 patients (80%) had evaluable angiographic data at 12 months. The angiographic restenosis rate at 12 months was 20% (15/75) in the cilostazol group versus 49% (38/77) in the noncilostazol group (P=0.0001) by intention-to-treat analysis. The cilostazol group also had a significantly higher event-free survival at 12 months (83% versus 71%, P=0.02), although cardiovascular event rates were similar in both groups. Conclusions— Cilostazol reduced angiographic restenosis after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00912756; and URL: https://www.umin.ac.jp. Unique identifier: UMIN000002091.

Impact of cilostazol after endovascular treatment for infrainguinal disease in patients with critical limb ischemia.

BACKGROUND Cilostazol reduces restenosis and repeat revascularization after endovascular therapy (EVT) in claudicant patients with femoropopliteal lesions. However, the efficacy of cilostazol in patients with critical limb ischemia (CLI) is unclear. Therefore, we investigated the effect of cilostazol on outcomes in patients with CLI. METHODS From January 2004 to December 2009, 618 patients (30.8% women, 356 treated with cilostazol, 72.4 ± 7.3 years old) with CLI underwent EVT for de novo infrainguinal lesions. Their data were retrospectively analyzed. The primary outcome measure was amputation-free survival (AFS), The secondary outcome measures were overall survival, limb salvage, freedom from repeat revascularization, and freedom from surgical conversion. Mean follow-up was 21 ± 14 months. RESULTS AFS and the limb salvage rate at 5 years were significantly higher in the cilostazol-treated group (47.7% vs 32.7%, P < .01; 86.6% vs 75.3%, P < .01; respectively). However, overall survival and freedom from repeat revascularization at 5 years did not differ significantly between the two groups (43.9% vs 46.0%, P = .24; 39.9% vs 31.8%, P = .21, respectively). Freedom from surgical conversion at 5 years was significantly higher in the cilostazol-treated group (91.0% vs 81.2%, P < .01). After correcting all end points with baseline variables, cilostazol was effective for prevention of AFS (hazard ratio [HR], 0.67; 95% confidential interval [CI], 0.49-0.91; adjusted P = .01) and improvement of limb salvage rate (HR, 0.42; 95% CI, 0.25-0.69; adjusted P < .01). There was no significant difference in overall survival, repeat revascularization, and surgical conversion between the groups. CONCLUSIONS Cilostazol may improve AFS and limb salvage rate after EVT for infrainguinal disease in patients with CLI.

3-Year Outcomes of the OLIVE Registry, a Prospective Multicenter Study of Patients With Critical Limb Ischemia: A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia.

OBJECTIVES This study sought to investigate the 3-year follow-up results of OLIVE registry patients. BACKGROUND Although favorable 12-month clinical outcomes after endovascular therapy (EVT) in OLIVE registry patients with critical limb ischemia (CLI) from infrainguinal disease have been reported, long-term results after EVT remain unknown. METHODS This was a prospective multicenter registry study that consecutively enrolled patients who received infrainguinal EVT for CLI. The primary outcome was 3-year amputation-free survival (AFS), whereas secondary outcome measures were 3-year freedom from major adverse limb events (MALE), wound-free survival, and wound recurrence rate. Prognostic predictors for each outcome were also elucidated by Cox proportional hazard regression analysis or the log-rank test. RESULTS The completion rate of 3-year follow-up was 95%. Three-year AFS, freedom from MALE, and wound-free survival rates were 55.2%, 84.0%, and 49.6%, respectively. Wound recurrence out to 3 years was 43.9%. After multivariable analysis, age (hazard ratio [HR]: 1.43, p = 0.001), body mass index ≤18.5 (HR: 2.17, p = 0.001), dialysis (HR: 2.91, p < 0.001), and Rutherford 6 (HR: 1.64, p = 0.047) were identified as predictors of 3-year major amputation or death. Statin use (HR: 0.28, p = 0.02), Rutherford 6 (HR: 2.40, p = 0.02), straight-line flow to the foot (HR: 0.27, p = 0.001), and heart failure (HR: 1.96, p = 0.04) were identified as 3-year MALE predictors. Finally, CLI due to isolated below-the-knee lesion was a wound recurrence predictor (HR: 4.28, p ≤ 0.001). Three-year survival, freedom from major amputation, and reintervention rates were 63.0%, 87.9%, and 43.2%. CONCLUSIONS In CLI patients with infrainguinal lesions, 3-year clinical results of EVT were reasonable despite high reintervention and moderate ulcer recurrence rate. (A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia [OLIVE 3-Year Follow-Up Study]; UMIN000014759).

Two-Year Life Expectancy in Patients With Critical Limb Ischemia

OBJECTIVES This study sought to estimate the 2-year life expectancy (2YLE) (estimated survival rate >50% at 2 years) in patients with critical limb ischemia (CLI) using the risk score based on predictors of all-cause mortality within 2 years. BACKGROUND It has been reported that 2YLE is one of the important factors in the decision making of the revascularization strategy. However, little is known about the probability and the prognostic factors of a 2YLE. METHOD This study was performed as a multicenter retrospective analysis. Between March 2004 and December 2011, 995 CLI patients with follow-up period >730 days undergoing endovascular therapy (EVT) were identified and analyzed. RESULTS Within 2 years, 412 patients (41%) died, and a cardiovascular cause accounted for 47% of deaths. On multivariate analysis, the independent prognostic factors were age 65 to 79 years (odds ratio [OR]: 1.9), 80 years of age or older (OR: 3.7), body mass index (BMI) 18.0 to 19.9 kg/m(2) (OR: 1.5), BMI <18.0 kg/m(2) (OR: 2.9), nonambulatory status (OR: 2.4), hemodialysis (OR: 2.1), cerebrovascular disease (OR: 1.6), left ventricular ejection fraction (LVEF) of 40% to 49% (OR: 1.8), LVEF <40% (OR: 2.6), Rutherford class 5 (OR: 1.9), and Rutherford class 6 (OR: 3.4). The 2-year survival rate in each risk score was calculated based on each OR (full score: 15 points). After that, 2YLE was estimated based on the survival rate in each risk score, the probability of a 2YLE of ≥8 points indicated a <50% probability of 2-year survival. CONCLUSIONS The independent prognostic factors for the 2YLE were age, BMI, nonambulatory status, hemodialysis, cerebrovascular disease, LVEF, and tissue loss. A 2YLE score of ≥8 points indicated a <50% probability of 2-year survival. This score seemed to be helpful for identifying CLI patients with a poor prognosis.

Increased levels of the oxidative stress marker, nitrotyrosine in patients with provocation test-induced coronary vasospasm

BACKGROUND Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of coronary vasospasm. However, it is not clear whether circulating biomarkers for oxidative stress are altered after coronary vasospasm. We investigated temporal changes in the levels of oxidative stress biomarkers after coronary vasospasm induced by intracoronary acetylcholine provocation testing, resulting in transient myocardial ischemia. METHODS AND RESULTS Thirty consecutive patients with suspected vasospastic angina pectoris (VSAP) were enrolled in the study. Patients were categorized into the VSAP-positive group (n=14) and the VSAP-negative group (n=16) on the basis of test results. Serum samples were examined for the levels of the oxidative stress markers 4-hydroxynonenal (HNE) and nitrotyrosine (NT) before, and 15min, 3h, and 12h after the provocation test. The serum HNE levels did not change in either group after the test. The serum NT levels in the VSAP-positive group significantly increased at 3h and 12h after the test (11.3±3.3μg/ml at 3h, p=0.015, and 12.1±5.7μg/ml at 12h, p=0.03), as compared with baseline (8.1±3.2μg/ml). In the VSAP-negative group, the serum NT levels significantly decreased from baseline at each of the 3 time points. CONCLUSIONS Serum NT significantly increased after coronary vasospasm induced by acetylcholine provocation, suggesting that serum NT could be a biomarker of transient myocardial ischemia and could contribute to the development of VSAP.

Serial cardiac influence of volume overload induced by interventional therapy for central venous stenosis or occlusion in chronic hemodialysis patients.

BACKGROUND Upper arm swelling and venous hypertension at arteriovenous fistula sites, and insufficiency of hemodialysis are induced by central venous lesions in chronic hemodialysis patients. Percutaneous transluminal angioplasty (PTA) for central venous lesions is first-choice treatment. Cardiac function can be evaluated by measuring the acute increase in venous return volume after PTA. METHODS We studied 6 cases of successful PTA for central venous stenotic or occluded lesions, and evaluated cardiac function by Swan-Ganz (SG) catheter and ultrasound echocardiography (UCG) at pre-, post-PTA, and on the following day. RESULTS Ejection fraction (EF) in 6 cases was 71.0 ± 5.5% on UCG. Two cases of subclavian venous stenosis, one case of subclavian venous occlusion, and three cases of brachiocephalic venous occlusion were enrolled. The reference diameter (RD) was 10.2 ± 4.9 mm, % diameter-stenosis (%DS) was 92.2 ± 12.2% at pre-PTA, and %DS at post-PTA was 21.7 ± 20.7%. There were no significant differences in pulmonary capillary-wedge, pulmonary artery, and right ventricular end-diastolic pressure in SG at pre- and post-PTA. The pressure of right atrium (RA) and cardiac output (CO) were significantly increased by PTA (RA pressure at pre-/post-PTA, 9.7 ± 2.9/11.7 ± 3.6 mmHg, p<0.05, CO at pre-/post-PTA 5.09 ± 2.07/5.45 ± 2.25 l/min, p<0.05). There were no significant differences in serial EF, left atrial and left ventricular diameters on UCG. However, the short-diameter of right ventricle (RV) and RA were significantly increased at post-PTA and recovered on the following day (RV short-diameter at pre-/post-/following-day PTA, 26.7 ± 3.5/32.5 ± 1.9/29.1 ± 1.7 mm, p<0.05; RA short-diameter at pre-/post-/following-day PTA, 30.2 ± 4.2/36.3 ± 2.4/32.1 ± 3.6mm, p<0.05). CONCLUSIONS Volume overload after PTA for central venous stenotic or occluded lesions in chronic hemodialysis patients resulted in increased RA and RV diameters. These changes were transient and completely recovered by the following day. PTA for central venous lesions in patients with normal EF can be performed without clinical cardiac problems.

Diurnal glycemic fluctuation is associated with severity of coronary artery disease in prediabetic patients: Possible role of nitrotyrosine and glyceraldehyde-derived advanced glycation end products.

BACKGROUND Glucose fluctuation (GF) is a risk factor for coronary artery disease (CAD). However, it remains unknown whether specific indices of GF are risk factors for CAD. Therefore, we evaluated the relationship between GF, as determined by a continuous glucose monitoring system (CGMS) or the glucose level at 2h after a 75-g oral glucose tolerance test (75g OGTT 120), and the severity of CAD in prediabetic patients. We also evaluated whether nitrotyrosine (NT) and glyceraldehyde-derived advanced glycation end-products (Glycer-AGE) were induced by GF. METHODS Twenty-eight prediabetic patients underwent coronary angiography (CAG), and the Gensini score and the SYNTAX score were evaluated as the severity of CAD, while the mean amplitude of glycemic excursions (MAGE) by CGMS and 75g OGTT 120 were evaluated. Serum NT and Glycer-AGE were measured. RESULTS The MAGE was closely associated with the Gensini score (r=0.742, p<0.001) and the SYNTAX score (r=0.776, p<0.001), respectively. The 75g OGTT 120 was not associated with the Gensini score (r=0.36, p=0.06), but it was significantly associated with the SYNTAX score (r=0.413, p=0.036). Multiple linear regression analysis showed that the MAGE was the only independent determinant for the severity of CAD. The levels of NT and Glycer-AGE were significantly higher in the high MAGE group than in the low MAGE group. CONCLUSIONS Diurnal GF is associated with the severity of CAD, even in prediabetic patients. GF, NT, and Glycer-AGE may play a pathological role in the progression of CAD.

Efficacy and Safety of Endovascular Therapy for Aortoiliac TASC D Lesions

Background: Although there is increasing evidence of the effectiveness of endovascular therapy for complex aortoiliac (AI) occlusive disease, it is not universally applied to TASC D lesions. Methods: A total of 2096 patients, 2601 limbs with AI occlusive disease, were enrolled. The lesions were categorized as TASC D (395) or TASC A-C (2206), and we compared baseline data, procedure, and follow-up result between the 2 groups. Results: The success rate of the procedure was significantly lower in the TASC D group (91.6% vs 99.3%, P < .01), and more procedure complications occurred in the TASC D group (11.1% vs 5.2%, P < .01). The results of a 5-year follow-up revealed no significant difference in primary patency (77.9% vs 77.1%, P = .17) and major adverse cardiovascular and limb events (MACLE; 30.5% vs 33.4%, P = .42) between the 2 groups. A multivariate analysis revealed complications and critical limb ischemia are independent predictors of MACLE in the TASC D group. Conclusion: The success rate of the procedure was lower in the TASC D group. Complications were more frequent in the TASC D group, and they were related to MACLE.

A case of coronary rupture and pseudoaneurysm formation after fracture of implanted paclitaxel-eluting stents

A 48-year-old man who had undergone implantation of two paclitaxel-eluting stents (PESs) at the right coronary artery was admitted to our hospital with progressive dyspnea. In the coronary care unit, he developed cardiogenic shock due to cardiac tamponade treated by pericardiocentesis. A coronary angiogram showed a large pseudoaneurysm at the site of the previously implanted stents, suggesting coronary rupture due to implanted stent fracture. The pseudoaneurysm was completely sealed by polytetrafluoroethylene-covered stent implantation. Although this case is very rare, coronary rupture by stent fracture should be considered when cardiac tamponade occurs after drug-eluting stent implantation, especially PES.