Recommendations for the management of the vascular involvement in Behçet's disease by the Japanese National Research Committee for Behçet's disease-secondary publication.

OBJECTIVES: This study aimed to develop clinical guidelines for the management of vascular Behçet's disease (BD) by the Behçet's Disease Research Committee of the Ministry of Health, Labour and Welfare of the Japanese Government. METHODS: A task force proposed clinical questions (CQs) concerning vascular BD based on a literature search. After screening, draft recommendations were developed for each CQ and brushed up in three blinded Delphi rounds, leading to the final recommendations. RESULTS: This study provides recommendations for 17 CQs concerning diagnosis and differential diagnoses, assessment of disease activity, and treatment. The guidelines recommend immunosuppressive treatments, for both arterial and venous involvement with active inflammation. Anticoagulation is also recommended for deep vein thrombosis except in high-risk patients. Surgical and endovascular therapies can be optional, particularly in patients with urgent arterial lesions undergoing immunosuppression. In addition, two sets of algorithms for diagnosis and treatment are shown for arterial and venous involvement. CONCLUSIONS: These recommendations are expected to serve as useful tools in the daily clinical practice of BD. This content has already been published in Japanese in the Guideline for the Management of Behçet's Disease 2020 and is submitted with permission from both the primary and secondary publishers.

Evaluation of Risk Factors for Major Amputation in Patients With Diabetes and Peripheral Artery Disease Receiving Antiplatelet Therapy　- Post Hoc Analysis of a Prospective Observational Multicenter Cohort Study (SEASON).

BACKGROUND: Guidelines for peripheral arterial disease (PAD) recommend long-term antiplatelet therapy in symptomatic patients to reduce cardiovascular morbidity and mortality risk. Although diabetes is a known risk factor for PAD, PAD has been undertreated in these patients. This study aimed to evaluate risk factors for major amputation in patients with diabetes undergoing antiplatelet therapy for PAD.Methods and Results:This retrospective analysis of a 2-year observational cohort study (1,745 clinics in Japan, September 2009-2013) evaluated predictors of amputation in patients with diabetes undergoing antiplatelet therapy for PAD. Among 4,016 eligible patients, 52 had an amputation during follow-up. Amputation risk (Cox regression analysis) was predicted at baseline by history of lower extremity revascularization/amputation (hazard ratio [HR]: 2.92; 95% confidence interval [CI]: 1.39, 6.14), chronic kidney disease (HR: 4.19; 95% CI: 1.95, 8.97), and comorbid cerebrovascular and heart disease (HR: 3.32; 95% CI: 1.19, 9.30), and was unaffected by choice of oral antiplatelet therapy. In patients with PAD and diabetes, amputation event rate was highest for those with ankle-brachial pressure index (ABI) <0.40 and progressively decreased at higher ABI cut-offs. CONCLUSIONS: These findings inform real-world understanding of PAD in diabetic patients receiving antiplatelet therapy in Japan, and showed that ABI <0.4 was the strongest risk factor for amputation.

Baseline Characterization of Japanese Peripheral Arterial Disease Patients　- Analysis of Surveillance of Cardiovascular Events in Antiplatelet-Treated Arteriosclerosis Obliterans Patients in Japan (SEASON).

BACKGROUND: Despite mounting evidence of increased cardiovascular events in patients with peripheral arterial disease (PAD), the overall incidence of cardiovascular events in PAD patients has not been fully clarified in Japan. The prospective Surveillance of cardiovascular Events in Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN (SEASON) is a prospective observational multicenter study and here we report the baseline clinical characteristics, including atherosclerosis risk factor prevalence, in PAD patients treated with antiplatelet agents. METHODS AND RESULTS: The SEASON registry enrolled 11,375 patients in 1,745 institutions and the data for 10,322 patients were analyzed. At baseline, the average age was 73.8±9.9 years, 60.0% were male and 83.9% were in Fontaine stage I or II. They had arteriosclerosis risk factors, such as current smoking (16.2%), hypertension (61.5%), diabetes mellitus (38.3%) and dyslipidemia (38.8%). There were complications including heart disease (29.7%), cerebrovascular disease (17.1%) and chronic kidney disease (14.3%). A subpopulation analysis revealed that the proportions of patients with risk factors were high in patients with lower ankle-brachial pressure index value. CONCLUSIONS: The baseline characteristics of the SEASON population demonstrate that real-world PAD patients have cardiovascular risk factors and comorbidities next to definite PAD patients. Further analysis of this database will contribute to understanding the real-world situation of PAD patients receiving antiplatelet therapy in Japan. (Circ J 2016; 80: 712-721).

Obstructive sleep apnea as a potential risk factor for aortic disease.

Obstructive sleep apnea (OSA) is not only a cause of hypertension; it also possibly affects the pathogenesis and progression of aortic disease because an inspiratory effort-induced increase in negative intrathoracic pressure generates mechanical stress on the aortic wall. The objective of the present study was to examine the incidence by location of OSA as a complication in patients with aortic aneurysm and patients with aortic dissection (AD). An overnight sleep study was conducted in the following study groups: the aortic disease group (n = 95) consisting of patients with thoracic aortic aneurysm (TAA, n = 32), patients with abdominal aortic aneurysm (AAA, n = 36), and patients with AD (n = 27); and a control group (n = 32), consisting of patients with coronary risk factors who were matched with the aortic disease group for age, gender, and body mass index (BMI). The 3% oxygen desaturation index (ODI) was significantly higher in all the TAA, AAA, and AD groups (P = 0.045, P = 0.003, and P = 0.005, respectively) than in the control group. The incidence of moderate to severe OSA [apnea hypopnea index (AHI) ≥15 events/h] was significantly higher in the first three groups (P = 0.026, P = 0.001, P = 0.003, respectively) than in the control group, while no significant difference was found between the TAA group and the AAA group with respect to these variables. Furthermore, no significant differences were found between the thoracic AD subgroup and the abdominal AD subgroup with respect to AHI and 3% ODI, as well as with respect to the incidences of moderate to severe OSA. Patients with TAA, patients with AAA, and patients with AD showed high incidences of moderate to severe OSA. Although this result suggests that OSA may be one of risks for aortic disease, unelucidated mechanism(s) other than negative intrathoracic pressure may be involved in the pathogenesis of aortic disease.

Spontaneous rupture of autogenous saphenous vein graft in bypass surgery for peripheral arterial disease possibly associated with collagen disease.

We encountered two cases of spontaneous rupture of a saphenous vein bypass graft for lower-leg peripheral arterial disease possibly associated with collagen disease. Rupture occurred 5 and 14 days postoperatively. Neither case had any signs of infection, graft degeneration, or evident injury, but both were associated with collagen disease diagnosed at another hospital. We believe that an association with collagen disease might have contributed to vein wall fragility in the present cases.

One-year atherothrombotic vascular events rates in outpatients with recent non-cardioembolic ischemic stroke: the EVEREST (Effective Vascular Event REduction after STroke) registry.

BACKGROUND: Patients with recent ischemic stroke may have higher risk of atherothrombosis than stable patients with established vascular events. Our aims were to investigate 1-year atherothrombotic vascular event rates and to assess the risk factors for recurrent ischemic stroke in this population. METHODS: This prospective cohort study was conducted between January 2007 and July 2009 at 313 hospitals in Japan. Outpatients who were at least 45 years of age and who had received oral antiplatelet therapy were enrolled within 2 weeks to 6 months from the last onset of noncardioembolic ischemic stroke. At 12 ± 3 months after enrollment, data on presence/absence of atherothrombotic vascular events were collected. The primary endpoint was the occurrence of fatal or nonfatal ischemic stroke. RESULTS: A total of 3452 patients were enrolled, and 3411 patients who had baseline data were included in the analysis. The 1-year event rate was 3.81% (95% confidence interval 3.15-4.48%) for fatal or nonfatal ischemic stroke and 0.84% (95% confidence interval 0.52-1.15%) for all-cause mortality. The annual rate of recurrent ischemic stroke was significantly higher in patients who had ischemic stroke at least twice than in patients who had first-ever ischemic stroke (5.02% vs 3.59%; P = .0313). In the multivariable Cox regression analysis, recurrent ischemic stroke was significantly associated with age (P = .0033), the presence of diabetes (P = .0129), and waist circumference ≥80 cm (P = .0056). CONCLUSIONS: Patients with recent ischemic stroke have a higher risk of stroke recurrence than stable patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry even though they received antiplatelet therapy. The rigorous management of risk factors is needed.

Staged hybrid repair using telescoped stent graft fixation for aortic arch and descending aortic aneurysms.

Staged repair of extensive thoracic aortic aneurysms is complicated, with a high incidence of interval rupture between stages. We describe the systematic staged hybrid procedure of a previous endovascular repair of a descending aortic aneurysm and open surgical repair of an aortic arch aneurysm. In the second-stage arch repair, the stent graft was easily retracted and fixed, without dissection, around the aortic arch aneurysm distal side. Extensive thoracic aortic aneurysms were managed without interim rupture or neurologic deficits. This approach avoided the potential for interim rupture because recovery from the first-stage endovascular repair was shorter than that from open repair.

Diabetes and old age could affect long-term patency of paramalleolar distal bypass for peripheral arterial disease in Japanese patients.

BACKGROUND: The results of paramalleolar distal bypass for critical limb ischemia in patients with peripheral arterial disease were reviewed to determine the factors affecting the long-term patency of this procedure in Japanese subjects. METHODS AND RESULTS: A total of 65 legs from 60 consecutive Japanese patients with critical limb ischemia who underwent distal bypass to the ankle were retrospectively reviewed. Postoperative graft patency, morbidity and mortality were analyzed. All patients were monitored during a mean follow-up period of 2.2 ± 1.7 years (median, 1.7 years). The accumulated primary and secondary patency rates were both 81.0% at 1 year and 78.7% at 3 and 5 years. The amputation-free rates and survival rates at 1 year, and 3 and 5 years were 94.5% and 82.6%, 82.6% and 88.1%, and 76.7% and 69.7%, respectively. The Cox proportional hazard model was used to determine factors contributing to long-term results. Age (odds ratio, 1.1; P<0.05) and diabetes (odds ratio, 18.0; P<0.05) were found to be the significant determinant factors of graft occlusion. No variables were found to be significant determinant factors of amputation-free or survival rates. CONCLUSIONS: Distal bypass to the paramalleolar tibial artery is an effective strategy for peripheral arterial disease with reasonable long-term reliability. Diabetes and old age were found to be the possible determinant factors of graft failure in Japanese patients.

Thoracic endovascular aortic repair with aortic arch vessel revascularization.

BACKGROUND: Revascularization of aortic arch vessels was performed with thoracic endovascular aortic repair (TEVAR) to preserve the endoprosthesis landing zone in 19 high-risk patients. METHODS: The operative procedure used was a bypass or transposition involving the common carotid and subclavian arteries. Homemade fenestrated stent-grafts, deployed in landing zone 0, were used for TEVAR. RESULTS: All lesions resolved without endoleaks. No perioperative deaths occurred; seven patients had postoperative complications. One patient with acute respiratory distress syndrome required reoperation to change the bypass route and permit tracheostomy. One patient died of pneumonia 2 months after treatment, after an anastomotic pseudoaneurysm and cerebral infarction developed and an operation was performed to obtain hemostasis. The procedure-related mortality was 5.3%. CONCLUSION: Aortic arch vessel revascularization before TEVAR may permit less invasive surgery, although careful patient selection is essential.

Intraoperative evaluation of blood perfusion by laser-assisted indocyanine green angiography after ex vivo vascular reconstruction of intrahilar renal artery aneurysm.

The surgical reconstruction of intrahilar renal artery aneurysms (RAAs) is a difficult surgery because of complex anatomy. We present a case of right intrahilar RAA diagnosed in a 67-year-old man. We performed ex vivo reconstruction using an organ preservation solution to prevent postoperative renal failure. We assessed graft patency and blood perfusion was assessed by laser-assisted indocyanine green angiography using the SPY system after autotransplantation. Postoperative renal insufficiency was not observed. The results demonstrate that ex vivo reconstruction of intrahilar RAAs using an organ preservation solution, and graft patency and blood perfusion evaluation using the SPY system are effective methods for preserving renal function.

Hybrid procedures combining conventional and thoracic endovascular aortic repair for thoracic aortic aneurysms.

PURPOSE: To minimize surgical invasiveness for extensive aortic aneurysms and expand the indications for thoracic endovascular aortic repair (TEVAR), we evaluated outcomes of hybrid procedures combining conventional surgical aortic repair and TEVAR for thoracic aortic aneurysms. METHODS: The following hybrid procedures were performed: second-stage TEVAR after total aortic arch replacement using the elephant trunk as the landing zone in 17 patients; and for multiple aortic aneurysms, vascular graft replacement and TEVAR in 13 patients, vascular graft replacement and TEVAR with bypass in 2 patients, and TEVAR with bypass in 23 patients. RESULTS: There were three (5.3%) hospital deaths, from serious complications including stroke, paraplegia, paraparesis, and aspiration pneumonia; and eight late deaths. There was only one aneurysm-related death, of a patient who underwent emergency surgery for an esophageal fistula resulting from enlargement of a residual false lumen of a thoracoabdominal aorta after second-stage TEVAR. CONCLUSION: Hybrid procedures minimize surgical invasiveness in thoracic aortic aneurysm repair, but further evaluation of a larger number of patients is necessary.

Successful treatment of multiple mycotic aortic aneurysms, using a hybrid procedure.

No generally accepted treatment of multiple mycotic aortic aneurysms of the thoracic and abdominal aorta has yet been established. We report a 67-year-old man with widespread mycotic aortic aneurysms previously treated for malignant lymphoma and interstitial pneumonia. He was successfully treated by a two-stage hybrid surgical procedure comprising open and endovascular methods. This is apparently the first report of repair of multiple mycotic aortic aneurysms using a hybrid procedure.

Endovascular repair of ascending aortic rupture: effectiveness of a fenestrated stent-graft.

PURPOSE: To present a technique for endovascular treatment using a fenestrated stent-graft in a patient with ascending aortic rupture in the setting of methicillin-resistant Staphylococcus aureus infection. CASE REPORT: A 62-year-old woman had undergone mastectomy and radiotherapy twice for breast cancer and then coronary artery bypass grafting (CABG). She developed sternal osteomyelitis 5 years after the CABG. Sternectomy and negative-pressure wound drainage were performed, but the infection did not resolve. Ascending aortic rupture occurred 5 months after sternectomy. Endovascular therapy was considered the only effective means of achieving hemostasis. A custom-designed fenestrated stent-graft was deployed from the ascending aorta to the proximal descending aorta via a femoral artery approach without transient cardiac arrest. Bleeding completely stopped after surgery. The postoperative course was uneventful, and the inflammatory activity subsided on antibiotic therapy. At 7 months after surgery, the patient's recovery has been uneventful. CONCLUSION: Rupture of the ascending aorta associated with infection was successfully treated by stent-graft repair. The use of a custom-made, fenestrated stent-graft was an effective, lifesaving procedure for the management of this ascending aortic lesion.

Patient-based outcomes using the Walking Impairment Questionnaire for patients with peripheral arterial occlusive disease treated with Lipo-PGE1.

BACKGROUND: Patients with peripheral arterial occlusive disease (PAD) experience deteriorating ambulatory function and consequently impaired quality of life (QOL). QOL in patients receiving prostaglandin E(1) in lipid microspheres (lipo-PGE(1); Liple) for the treatment of PAD has not been evaluated using the Japanese version of the Walking Impairment Questionnaire (WIQ). METHODS AND RESULTS: Data from 169 patients (98 men, 71 women; mean [median] age, 74+/-10 [74] years) with an ankle-brachial pressure index <0.9 were analyzed. WIQ scores and symptom scores significantly improved after lipo-PGE(1) treatment (P<0.01). Physicians' assessments of global improvement significantly correlated with all 4 WIQ subscales (R< or =0.31). CONCLUSIONS: WIQ is a valid tool for evaluating therapeutic response in patients with PAD. Lipo-PGE(1) improves QOL as evaluated by patients themselves.

A case of abdominal aortic aneurysm associated with L-shaped crossed-fused renal ectopia.

Genitourinary anomalies are a tremendous challenge for the vascular surgeon, especially when dealing with an abdominal aortic aneurysm. We report a case of crossed-fused renal ectopia, a rare anomaly accompanied by abdominal aortic aneurysm. Bilateral renal arteries and one aberrant artery from the right common iliac artery supply the ectopic kidney. Because renal ischemia during aortic reconstruction can be a serious problem, we reconstructed a temporary right axillo-left renal artery bypass graft first, then reimplanted the aberrant renal artery. When choosing the procedure for renal preservation, preoperative multidetector-row computed tomography was useful to plan the operative strategy.

Endovascular stenting for popliteal vascular entrapment is not recommended.

Endovascular techniques are often applied, but they have occasionally been reported in the treatment of popliteal vascular entrapment (PVE). A case of bilateral PVE is presented with an acute occlusion of the right popliteal artery. This was twice unsuccessfully treated with arterial recanalization and stenting at another Institution. The patient required an arterial reconstruction with his reversed saphenous vein, in addition to resection of the medial gastrocnemius muscle laterally inserted on his right limb. The left limb was treated with a simple myotomy. Recanalization and stenting is not recommended for PVE treatment.

Left atrial myxoma associated with acute myocardial infarction and multiple cerebral infarctions: Report of a case.

We report a case of left atrial myxoma associated with acute myocardial infarction (AMI) in a 63-year-old man. Percutaneous coronary intervention was performed immediately, and we removed white intracoronary particles by using a thrombectomy catheter. The postinterventional course was uneventful; however, on hospital day 5, pathological examination revealed platelet thrombus and myxomatous tissue from the particles aspirated by thrombectomy catheter, and transesophageal echocardiography showed a gelatinous mass in the left atrium. Based on these findings, we diagnosed AMI caused by coronary embolization from a left atrial myxoma, and excision of the myxoma was scheduled. However, preoperative magnetic resonance imaging revealed multiple subacute cerebral infarctions, and the tumor was successfully excised on hospital day 13. Although coronary embolization induced by cardiac myxoma is rare, it should be considered in a young to middle-aged patient presenting with signs of AMI without coronary risk factors.

Study design of SEASON registry: prospective Surveillance of cardiovascular Events in an Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN )SEASON).

Antiplatelet therapy is widely performed for arteriosclerosis obliterans (ASO) to relieve ischemic symptoms and prevent cardiovascular events. However, the overall rate of cardiovascular events in patients with ASO under treatment with antiplatelet agents has not been fully investigated in Japan. The SEASON registry is a nationwide observational prospective cohort study designed to compile data from over 2,000 institutions across Japan, whose aims are to (1) understand the current status for the management of ASO and clarify the incidence of cardiovascular events in patients with ASO undergoing antiplatelet therapy, and (2) compare the effectiveness of sarpogrelate, a 5-HT(2A) receptor antagonist, in decreasing the event rate with those of other antiplatelet agents [UMIN ID: UMIN000003385]. The registry will recruit approximately 10,000 patients receiving antiplatelet therapy (8,000 patients for sarpogrelate and 2,000 for other antiplatelet agents), and the patients will be followed every 6 months during a two-year follow-up period. The investigators plan to report all cardiovascular events and exacerbations of ASO. Analysis focusing on the sarpogrelate-treated subgroup will also be performed. Exploratory analysis will be performed to determine the clinical characteristics of the patients and to elucidate the relationships between risk factors and cardiovascular events. The SEASON registry is the first attempt to create a nationwide database regarding the incidence of cardiovascular events in 10,000 ASO patients in Japan. In addition, it ultimately may enable us to conclude that sarpogrelate prevents cardiovascular events. Information on the severity and risk factors in ASO patients in the clinical settings will be applicable to epidemiological analysis.

[Revascularization for the aortoiliac regions of peripheral arterial disease].

As far as the indications for revascularization in the abdominal aortoiliac region are concerned, endovascular therapy is recommended for TASC II type A and type B lesions, and surgical bypass is recommended for TASC II type C and type D lesions. As stents have been developed and used more frequently in recent years, the results for endovascular therapy have dramatically improved, and its indications are beginning to be expanded. Endovascular therapy is the first-live therapy for stenotic lesions smaller than 10 cm in length or bilateral common or external iliac artery occulusion (type A and type B lesions). For highly skilled surgeons, endovascular therapy is the first-line therapy for type C and type D lesions exclude aorta and common femoral artery lesions. Therefore, when performing endovascular therapy for type C and type D lesions, it is necessary to sufficiently evaluate not only the skill of the surgeon, patient risk and QOL, but also revascularization. Furthermore, it is imperative to consider therapeutic options when endovascular therapy ends in failure.