Previous studies have reported the efficacy and safety of therapeutic angiogenesis through bone marrow-derived mononuclear cell (BM-MNC) implantation in patients with no-option chronic limb-threatening ischemia (CLTI) from atherosclerotic lower extremity artery disease (LEAD). However, uncertain clinical prognostic factors impact treatment outcomes. This study aimed to elucidate the long-term outcomes of patients with atherosclerotic LEAD-derived no-option CLTI after BM-MNC implantation and to identify prognostic factors.In this retrospective, single-center, observational study, the primary endpoints included the long-term prognosis of BM-MNC implantation and factors influencing 1-year outcomes. A total of 92 limbs in 84 patients were analyzed in the final cohort (mean age: 67 years; male, 65%). The 5- and 10-year overall survival rates were 50.0% and 31.0%, respectively, while the 5- and 10-year amputation-free survival rates were 37.6% and 23.3%, respectively. Multivariate logistic analysis linked all-cause mortality to age ≥ 70 years, hemodialysis, smoking, and a controlling nutrition status score ≥ 5. Major amputation or mortality was associated with male sex, hemodialysis, and C-reactive protein levels ≥ 3.0 mg/dL. No adverse events were associated with therapeutic angiogenesis.These findings endorse the feasibility and safety of BM-MNC implantation for patients with no-option CLTI due to atherosclerotic LEAD. Moreover, the study highlights the significance of several prognostic factors, including advanced age, hemodialysis, smoking, and inflammatory markers, in influencing the long-term outcomes of this treatment.

Background:Basic fibroblast growth factor (bFGF) is an angiogenic factor with a short half-life. Because recombinant bFGF is in clinical use, we hypothesized that the localization of recombinant bFGF with atelocollagen would have angiogenic effects at the injection site in normal and hind limb ischemic animal models. Methods and Results:We administered the recombinant bFGF with atelocollagen intramuscularly to hind limbs in normal rabbits or in a mouse model of femoral artery ligation to explore the pharmacological action for ischemia. We evaluated blood flow in the ischemic/normal limb using laser speckle perfusion imaging and the density of blood vessels by pathological examination. At the administration site in normal rabbits, a significant increase in the number of blood vessels was noted at 14 days post-administration of recombinant bFGF with atelocollagen compared with saline or atelocollagen alone. In mice with femoral artery ligation, blood flow and vessels in the ischemic hind limb increased at 2 weeks after injection and more at 4 weeks after injection, and the effect was most significant in mice administered 100 μg of recombinant bFGF with 3% of atelocollagen. Conclusions:Intramuscular administration of recombinant bFGF with atelocollagen induced angiogenesis between 2 and 4 weeks in both normal and ischemic hind limbs.

Background Acute mesenteric ischemia is rare, and few large‐scale trials have evaluated endovascular therapy (EVT) and open surgical revascularization (OS). This study aimed to assess clinical outcomes after EVT or OS for acute superior mesenteric artery occlusion and identify predictors of mortality and bowel resection. Methods and Results Data from the Japanese Registry of All Cardiac and Vascular Diseases‐Diagnosis Procedure Combination (JROAD‐DPC) database from April 2012 to March 2020 were retrospectively analyzed. Overall, 746 patients with acute superior mesenteric artery occlusion who underwent revascularization were classified into 2 groups: EVT (n=475) or OS (n=271). The primary clinical outcome was in‐hospital mortality. The secondary outcomes were bowel resection, bleeding complications (transfusion or endoscopic hemostasis), major adverse cardiovascular events, hospitalization duration, and cost. The in‐hospital death or bowel resection rate was ≈30%. In‐hospital mortality (22.5% versus 21.4%, P =0.72), bowel resection (8.2% versus 8.5%, P =0.90), and major adverse cardiovascular events (11.6% versus 9.2%, P =0.32) were comparable between the EVT and OS groups. Hospitalization duration in the EVT group was 6 days shorter than that in the OS group, and total hospitalization cost was 0.88 million yen lower. Interaction analyses revealed that EVT and OS had no significant difference in terms of in‐hospital death in patients with thromboembolic and atherothrombotic characteristics. Advanced age, decreased activities of daily living, chronic kidney disease, and old myocardial infarction were significant predictive factors for in‐hospital mortality. Diabetes was a predictor of bowel resection after revascularization. Conclusions EVT was comparable to OS in terms of clinical outcomes in patients with acute superior mesenteric artery occlusion. Some predictive factors for mortality or bowel resection were obtained. Registration URL: www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000045240.

Abstract Background The etiology of acute limb ischemia (ALI) involves embolism as well as atherosclerotic thrombosis. Although endovascular therapy (EVT) or Fogarty thrombectomy (Fogarty TE) is the recommended revascularization method for ALI, treatment choice based on patient characteristics remains controversial. Purpose This study aimed to evaluate the differences in clinical outcomes between primary treatments and identify predictive factors affecting clinical outcomes in patients with ALI. Methods This retrospective study used data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database, from April 2012 to March 2020. We analyzed 18,701 patients with ALI and categorized them into medication and invasive treatment groups (EVT alone, Fogarty TE alone, bypass surgery alone, and hybrid treatment). The EVT-alone and Fogarty TE-alone groups were compared after propensity score matching, considering 19 clinically relevant covariates. The primary outcomes were in-hospital mortality, major amputation, and bleeding complications (anemia requiring transfusion or endoscopic hemostasis). The secondary outcomes were major adverse cardiovascular events (myocardial infarction, coronary intervention, heart failure, stroke, and cerebral hemorrhage), major amputation and/or death, hospitalization duration, and total cost during hospitalization. Results The EVT-alone group had more patients at a higher risk of atherosclerotic disease, including peripheral artery disease (PAD), chronic kidney disease (CKD), or hemodialysis. The Fogarty TE-alone group had more patients at a higher risk of embolism, including AF or AFL. After propensity score matching, in-hospital mortality (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.29–1.92, p<.0001), bleeding complications (OR: 1.28, 95% CI: 1.12–1.46, p=0.0002), and major amputation rates (OR: 1.44, 95% CI: 1.17–1.76, p=0.0004) were significantly higher in the EVT-alone group than in the Fogarty TE-alone group. Major amputation and/or death rates and total hospitalization costs were higher in the EVT-alone group than in the Fogarty TE-alone group. In interaction analyses, EVT demonstrated a favorable trend of lower risks of death and/or major amputation in patients with PAD, CKD, and diabetes mellitus (all risk factors for atherosclerotic disease), especially in those with PAD and CKD. Conclusions Fogarty TE may be the preferred primary treatment for patients with ALI, particularly those without PAD or CKD.Study flowchartForest plot analyzing interaction effect

Background: The etiology of acute limb ischemia (ALI) has been often reported to be embolism caused by atrial fibrillation (Af) and/or atrial flutter (AFL), and thrombosis caused by atherosclerosis. Although endovascular therapy (EVT) or fogarty thrombectomy (Fogarty) is recommended as a primary treatment for patients with ALI, which treatment should be chosen is still controversial. Aim: To evaluate differences of clinical outcomes between primary treatments for patients with ALI, and identify prognostic predictors. Methods: This was a retrospective study based on the database in the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Figure.1 showed the flow chart of this study. Comparison with EVT-alone and Fogarty-alone group was analyzed using propensity score matching with 16 clinically relevant covariates. Clinical outcomes were death, major adverse cardiovascular events (MACE; myocardial infarction, coronary intervention, heart failure, stroke, cerebral hemorrhage), bleeding complications with bleeding academic research consortium (BARC) type 3-5, and any amputation. Results: Figure2-4 showed the results of this study. Figure.3 demonstrated that bleeding complications and any amputation in Fogarty-alone group were significantly less than EVT-alone group. Figure.4 revealed that Fogarty tended to decrease an amputation-free survival rate in ALI patients who had no history of peripheral artery disease (PAD) and not administered an antiplatelet before onset. Conclusions: Fogarty should be selected as the primary treatment as much as possible for ALI patients, especially those without PAD.

BACKGROUND: Although drug-coated balloon (DCB)-based stent-less percutaneous coronary intervention (PCI) for de-novo lesions has attracted more attention, outcomes of the DCB procedure for hemodialysis (HD) patients are reported to be inferior to those for non-HD patients, similarly to drug-eluting stent (DES). Recent several reports have shown that rotational atherectomy (RA) followed by DCB treatment (RA/DCB) could be an option of revascularization strategy particularly for calcified de-novo lesions even in the new-generation DES era; however, efficacy of the RA/DCB procedure for HD patients remains unclear.METHODS: A total of 47 consecutive cases (53 lesions) undergoing RA/DCB for de-novo lesions were enrolled. According to the presence/absence of HD at baseline, the 47 cases were divided into the HD cases (N.=16) and the non-HD cases (N.=31), and the 53 lesions were divided into the HD lesions (N.=20) and the non-HD lesions (N.=33).RESULTS: The HD cases had a significantly lower prevalence of dyslipidemia and smoking than the non-HD cases. Final RA burr size, DCB diameter used, and angiographic success rate of PCI did not significantly differ between the 2 groups. Preprocedural, post-procedural, and follow-up QCA parameters were also similar between the 2 groups. Twelve-month clinical outcomes were comparable between the 2 groups.CONCLUSIONS: Mid-term outcomes of stent-less PCI using RA/DCB for de-novo lesions in HD patients might be comparable to those in non-HD patients, suggesting efficacy of pretreatment of RA prior to DCB treatment in HD patients.

Background: Thromboangiitis obliterans (TAO) can develop critical limb-threatening ischemia (CLTI). Despite conventional treatments, such as smoking cessation or revascularization, young patients require limb amputation. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation has demonstrated long-term efficacy and safety in patients with CLTI, particularly those with TAO. To expand BM-MNC implantation in clinical practice, further evidence is required in CLTI patients with TAO. We aimed to determine the efficacy of BM-MNC implantation in a prospective trial. Methods: This multicenter, prospective, interventional trial was performed under an advanced medical care program. We enrolled 22 patients with CLTI and skin perfusion pressure (SPP) <30 mmHg; they underwent BM-MNC implantation within 28 days (Figure.1). The follow-up period was 180 days, and the primary endpoint was an improvement in the SPP value in the affected target limb 180 days after the implantation. One patient dropped out from the follow-up. Results: The mean age was 47.6 years (male: 90.5%, Fontaine classification IV: 57.1%). The SPP value significantly improved on day 180 (p<0.001) (Figure. 2). The secondary endpoints, i.e., numerical rating scale scores and transcutaneous oxygen pressure values significantly improved within day 180. The 3-year major amputation-free and overall survival probability in the safety analysis set were 95.5% and 89.5%, respectively (Figure. 3). No severe adverse events occurred. Conclusions: We believe that the BM-MNC implantation will likely become a feasible and safe therapy for CLTI patients caused by TAO.

BACKGROUND:Several recent reports have shown that a stentless interventional procedure using rotational atherectomy followed by drug-coated balloon (DCB) treatment (RA/DCB) is a potent revascularization therapy for calcified de novo lesions even in the new-generation drug-eluting stent era; however, the role of the RA/DCB procedure for noncalcified de novo lesions remains unclear. METHODS:A total of 47 consecutive patients (53 lesions) who underwent RA/DCB for coronary de novo lesions were enrolled. According to the presence or absence of severe calcification at target lesions on fluoroscopy, the 47 patients were divided into the noncalcified cases (n = 12) and the calcified cases (n = 35), and the 53 lesions were divided into the noncalcified lesions (n = 14) and the calcified lesions (n = 39). RESULTS:The noncalcified cases tended to have a higher frequency of bleeding risk and had a significantly lower prevalence of dual antiplatelet therapy compared with the calcified cases. The main lesion-specific factors for the RA/DCB procedure among the noncalcified lesions were presence of left circumflex coronary artery ostial lesion. The final burr size, DCB diameter used, and angiographic success rate did not significantly differ between the 2 groups. The noncalcified lesions had a larger reference diameter and a shorter lesion length than the calcified lesions, whereas acute gain and late lumen loss did not differ between the 2 groups. Nine-month clinical outcomes were comparable between the 2 groups. CONCLUSIONS:Under drug-eluting stent-unsuitable clinical or lesion conditions, acute and midterm outcomes of RA/DCB for noncalcified de novo lesions might be comparable with those for calcified de novo lesions.