Comparison of Clinical Outcomes in Patients with Acute Lower Limb Ischaemia Undergoing Endovascular Therapy and Open Surgical Revascularisation: A Large Scale Analysis in Japan.

OBJECTIVE: The recommended revascularisation methods for acute limb ischaemia (ALI), which is caused by embolism and atherosclerotic thrombosis, include endovascular therapy (EVT) and open surgical revascularisation (OSR); however, treatment choices based on patient characteristics remain controversial. This retrospective analysis from the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination database (April 2012 to March 2020) evaluated differences in clinical outcomes and identified prognostic predictors in patients with ALI. METHODS: This study analysed 10 977 patients with lower limb ALI. EVT was defined as catheter directed thrombolysis, percutaneous thrombectomy, or percutaneous angioplasty with balloon dilatation and or stenting. OSR was defined as Fogarty thrombectomy, bypass surgery, or thromboendarterectomy. The EVT and OSR groups were compared after propensity score matching (PSM) considering ten clinical covariates. RESULTS: The EVT group had more patients at higher risk of atherosclerotic disease than the OSR group. The OSR group had more patients at a higher risk of embolism, including atrial fibrillation and atrial flutter, than the EVT group. In the EVT group, 20.4% of patients underwent catheter directed thrombolysis using urokinase, the only thrombolytic agent available in Japan that is covered under insurance. After PSM, in hospital mortality (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.11 - 1.59; p = .002), major amputation rate (OR 1.43, 95% CI 1.19 - 1.72; p < .001), major amputation and or death rate (OR 1.42, 95% CI 1.24 - 1.62; p < .001), and total hospitalisation cost (1.16 vs. 0.97 million yen; p < .001) were statistically significantly higher in the EVT group than in the OSR group. In interaction analyses, peripheral artery disease (PAD) was a factor responsible for reducing OSR efficacy in terms of major amputation and or death rate (with PAD, OR 0.94, 95% CI 0.68 - 1.29; without PAD, OR 1.56, 95% CI 1.34 - 1.82; p = .004). CONCLUSIONS: In Japan, EVT was a less effective primary treatment for patients with ALI than OSR, except for those with PAD.

Comparison of Endovascular Therapy and Open Surgical Revascularization in Patients With Acute Superior Mesenteric Artery Occlusion: A Large-Scale Analysis Based on the JROAD-DPC Database.

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.

A Multicenter Prospective Interventional Trial of Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans.

BACKGROUND: Thromboangiitis obliterans (TAO) can lead to the development of critical limb-threatening ischemia (CLTI). Despite conventional treatments, such as smoking cessation or revascularization, young patients (<50 years) still require limb amputation. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation has been tested and shown to have reasonable efficacy in CLTI. In this multicenter prospective clinical trial, we evaluated the safety and efficacy of BM-MNC implantation in CLTI patients with TAO.Methods and Results: We enrolled 22 CLTI patients with skin perfusion pressure (SPP) <30 mmHg. The primary endpoint of this trial is the recovery of SPP in the treated limb after a 180-day follow-up period. Secondary endpoints include the pain scale score and transcutaneous oxygen pressure (TcPO2). One patient dropped out during follow-up, leaving 21 patients (mean age 48 years, 90.5% male, Fontaine Class IV) for analysis. BM-MNC implantation caused no serious adverse events and increased SPP by 1.5-fold compared with baseline. Surprisingly, this effect was sustained over the longer term at 180 days. Secondary endpoints also supported the efficacy of this novel therapy in relieving pain and increasing TcPO2. Major amputation-free and overall survival probabilities at 3 years among all enrolled patients were high (95.5% and 89.5%, respectively). CONCLUSIONS: BM-MNC implantation showed safety and significant efficacy in CLTI patients with TAO.

Impact of Door-to-Balloon Time Reduction Depending on the Killip Classification in Patients with ST-Segment Elevation Myocardial Infarction Transported by Emergency Medical Services.

The coronavirus disease 2019 pandemic occurred in several countries, making the conventional medical system difficult to maintain. Recent recommendations aim to prevent nosocomial infections and infections among health care workers. Therefore, establishing a cardiovascular medical system under an emergency for patients with ST-segment elevation myocardial infarction (STEMI) is desired. This study aimed to determine the relationship between prognosis and door-to-balloon time (DBT) shortening based on the severity on arrival.This retrospective, multi-center, observational study included 1,127 consecutive patients with STEMI. These patients were transported by emergency medical services and underwent primary percutaneous coronary intervention. Patients were stratified according to the Killip classification: Killip 1 (n = 738) and Killip ≥ 2 (n = 389) groups.Patients in the Killip ≥ 2 group were older, with more females, and more severity on arrival than those in the Killip 1 group. The 30-day mortality rate in the Killip 1 and Killip ≥ 2 groups was 2.2% and 18.0%, respectively. The Killip ≥ 2 group had a significant difference in the 30-day mortality between patients with DBT ≤ 90 minutes and those with DBT > 90 minutes; however, this did not occur in the Killip 1 group. Furthermore, multivariate analysis revealed that DBT ≤ 90 minutes was not a significant predictive factor in the Killip 1 group; however, it was an independent predictive factor in the Killip ≥ 2 group.DBT shortening affected the 30-day mortality in STEMI patients with Killip ≥ 2, although not those with Killip 1.

New risk factors for early- and late-onset cardiac rupture in ST-elevation myocardial infarction patients after primary percutaneous coronary intervention.

BACKGROUND: Cardiac rupture (CR) is a catastrophic complication of acute myocardial infarction. Primary percutaneous coronary intervention (pPCI) reduces the incidence of CR. This study aimed to investigate the clinical risk factors and characteristics of CR after pPCI. METHODS: This was a retrospective, case-control, multicenter study. We enrolled 2444 consecutive patients with ST-elevation myocardial infarction (STEMI) who had undergone pPCI between 2009 and 2015; 33 patients experienced CR (1.35%): 19 were assigned as early CR (≤72 h) and 14 as late CR (>72 h). The 132 controls were randomly selected from the 2411 STEMI patients without CR, by matching institutions at a 1:4 ratio. RESULTS: Multivariate logistic regression revealed that female sex, acute hyperglycemia, thrombocytopenia (platelets <15 × 104/µL), and incomplete revascularization [post-PCI thrombolysis in myocardial infarction (TIMI) <3] were independent risk factors for CR (p<0.05). Older age, female sex, and emergency surgical repair were strongly associated with in-hospital death, which occurred in 66.7% of CR patients (p<0.05). Univariate logistic regression adjusted for age and sex revealed that low systolic blood pressure, anterior infarction, acute hyperglycemia, Killip class >1, and post-PCI TIMI <3 were significantly associated with early CR, and that Killip class >1 and thrombocytopenia were strongly associated with late CR. Early CR occurred more frequently between 12:00 and 21:00 h, whereas the peak incidence of late CR was bimodal between 6:00-12:00 and 21:00-24:00 h. CONCLUSIONS: In STEMI patients after pPCI, acute hyperglycemia and thrombocytopenia are new risk factors for early and late CR, respectively. Clinical risk factors and time of occurrence of early and late CR may differ in the PCI era.

Impact of Therapeutic Angiogenesis Using Autologous Bone Marrow-derived Mononuclear Cell Implantation in Patients with No-option Critical Limb Ischemia.

Recently, the limb salvage rate of patients with critical limb ischemia (CLI) has been improved due to the development of revascularization and wound care treatment. However, many patients with CLI are refractory to standard treatments, including revascularization such as endovascular treatment or surgical bypass. Establishment of a new cell therapy is required to improve the limb salvage rate and prognosis in patients with CLI. In 1997, endothelial progenitor cells were found to be derived from the bone marrow to circulate as CD34 surface antigen positive cells in peripheral blood and to affect therapeutic angiogenesis in ischemic tissues. Later, therapeutic angiogenesis using autologous bone marrow-derived mononuclear cell (BM-MNC) implantation was performed for patients with no-option CLI in clinical practice. Several reports showed the safety and efficacy of the BM-MNC implantation in patients with CLI caused by arteriosclerosis obliterans, thromboangiitis obliterans (TAO), and collagen diseases. In particular, in patients with CLI caused by TAO, limb salvage rate was significantly improved compared with standard treatments. The BM-MNC implantation may be feasible and safe in patients with no-option CLI. Here, we review the efficacy of BM-MNC implantation in no-option CLI, with a focus on therapeutic angiogenesis.

Effectiveness of high flow-volume intermittent hemodiafiltration during and after intervention to prevent contrast-induced nephropathy in patients with advanced chronic kidney disease: A pilot study.

OBJECTIVES: We analyzed the effect of high flow-volume intermittent hemodiafiltration (HF-IHDF) on patients with advanced chronic kidney disease (CKD) undergoing procedures requiring administration of contrast medium. BACKGROUND: There is no effective method for preventing contrast-induced nephropathy (CIN), especially in patients with advanced CKD. We established HF-IHDF as a renal protective therapy with a filtration flow rate up to 5 times greater than standard continuous HDF. In this study, we tested whether HF-IHDF could prevent CIN in patients with advanced CKD more effectively than saline hydration only. METHODS: We retrospectively analyzed the incidence of CIN and clinical outcomes up to 1 year after performance of a procedure in 76 patients with advanced CKD. HF-IHDF was performed from just before the procedure until 2.5 hr after it. Hydration with 0.9% saline was also administered. RESULTS: The incidence of CIN was significantly lower in the HF-IHDF group than the saline group 2-3 days (0%, 0/76 patients vs. 9.3%, 5/54 patients; p < .05) and 1 month (3.9%, 3/76 patients vs. 14.8%, 8/54 patients; p < .05) after intervention. No difference between the two groups was detected in the proportion of patients requiring permanent hemodialysis within 1 year after intervention or the 1 year mortality rate. However, the number of patients free from progression of renal dysfunction after 1 year of follow-up was significantly higher in the HF-IHDF group (86.8%, 66/76 patients vs. 64.8%, 35/54 patients; p < .01). CONCLUSIONS: HF-IHDF during and after interventional procedure requiring administration of contrast medium may prevent CIN in patients with advanced CKD.

Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans　- Study Protocol for a Multicenter Prospective Interventional Trial.

Background: Patients with thromboangiitis obliterans (TAO) can develop critical limb-threatening ischemia (CLTI) and require limb amputation. Smoking cessation and exercise therapy are recommended as standard treatments, and revascularization by bypass surgery or endovascular therapy (EVT) is required for patients with CLTI. However, there are many cases in which revascularization is difficult because of vascular characteristics, and the patency rate after revascularization remains unsatisfactory. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation is used clinically, with many trials demonstrating long-term efficacy and safety of the technique in patients with CLTI, especially that caused by TAO. To expand the use of BM-MNCs implantation in clinical practice, further evidence is required in patients with CLTI caused by TAO. Methods and Results: This trial is a multicenter, prospective, non-randomized interventional trial of an Advanced Medicine B treatment approach. We aim to enroll 25 patients aged 20-80 years with Fontaine classification Stage III or IV, who will undergo BM-MNC implantation. The primary endpoint is the improvement in skin perfusion pressure of the target limb 180 days after BM-MNC implantation, whereas secondary endpoints are improvements in rest pain or ulcer size. We will also investigate rates of major or minor amputation, survival, and adverse events during follow-up. Conclusions: BM-MNC implantation is expected to be an efficacious and feasible treatment for patients with CLTI caused by TAO.