Background:Despite the growing knowledge regarding optimal treatments for critical limb ischemia (CLI), there are still a considerable number of patients who have to undergo major limb amputation. Intramuscular injection of autologous adipose-derived regenerative cells (ADRCs) in these patients has shown therapeutic potential in improving tissue ischemia, in both preclinical and initial pilot studies. Here, we present a clinical protocol for ADRCs use in a multicenter trial.
Methods and Results:The TACT-ADRC multicenter trial is a prospective, interventional, single-arm, open-labeled study at 8 hospitals in Japan, investigating the safety and feasibility of intramuscular injections of ADRCs and testing the hypothesis that this treatment promotes neovascularization and improves major amputation-free survival rates in patients with CLI who have no other treatment option. 40 patients with CLI will be enrolled and followed up from November 2015 to November 2020. Freshly isolated autologous ADRCs will be injected into the target ischemic limbs. Survival rate, adverse events, major limb amputation, ulcer size, 6-min walking distance, numerical rating scale, ankle–brachial pressure index, skin perfusion pressure and digital subtraction angiography will be evaluated at baseline and during 6 months’ follow-up.
Conclusions:This trial will demonstrate whether implantation of autologous ADRCs is a safe and effective method for therapeutic angiogenesis, resulting in an improvement in major amputation-free survival rates in patients with CLI.
Background:In surgical aortic valve replacement (SAVR), coronary arteries are routinely assessed by transesophageal echocardiography (TEE) to prevent undesirable complications. This study evaluated the capabilities and pitfalls of TEE assessment.
Methods and Results:Of 147 consecutive SAVR patients undergoing aortic stenosis, the TEE records for 130 patients, in which the procedures were conducted by a single examiner, were analyzed retrospectively regarding data acquisition and the accuracy of detecting an anomalous origin, high or low takeoff, ostial diameter, and short left main truncus (LMT). The left and right coronary arteries could be visualized in every patient. A left coronary ostium >5 mm was found in 33 patients (25.4%). TEE revealed an anomalous origin in 2 patients (1.5%) that had not been diagnosed, but missed it in another patient. High takeoff was noted in 11 patients (8.3%), often associated with aortic disease necessitating aortic repair. In one such patient, occlusion of the right coronary artery was detected, necessitating coronary revascularization. Short LMT was found in 15 patients (11.8%) but misdiagnosed due to artifact in 1. During selective cardioplegia, malperfusion of the left anterior descending artery due to deep cannula placement was detected.
Conclusions:TEE provides fairly accurate assessment in SAVR, including detection of undiagnosed pathologies or pitfalls related to coronary arteries, although misdiagnosis due to artifacts should be kept in mind.
Background:Few studies have investigated the importance of glycemic control in patients with diabetes mellitus (DM) for reducing the incidence of late target lesion revascularization (TLR) after implantation of new-generation drug-eluting stents (DES).
Methods and Results:We retrospectively identified 1,568 patients who underwent new-generation DES implantation. Patients were divided into 3 groups based on diabetic status and glycemic control 1 year after the procedure: those without DM (non-DM group; n=1,058) and those with DM at follow-up with either good (HbA1c <7%; n=328) or poor (HbA1c ≥7%; n=182) control. The cumulative 5-year incidence of clinically driven late TLR after the index procedure was significantly higher in DM with poor control at follow-up than in those with good control at follow-up or non-DM (14%, 4.8%, and 2.9%, respectively; P<0.0001). Multivariate analysis revealed that poor control at follow-up was significantly associated with a higher risk of clinically driven late TLR compared with the non-DM group (hazard ratio [HR] 4.58, 95% confidence interval [CI] 2.50–8.16, P<0.0001). However, good control at follow-up group was not associated with a higher risk of clinically driven late TLR compared with the non-DM group (HR 1.35, 95% CI 0.68–2.56, P=0.38).
Conclusions:DM patients with poor glycemic control at follow-up had a significantly higher risk of clinically driven late TLR than non-DM patients.
Background:Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown.
Methods and Results:Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P<0.001), but there was no significant difference in embolic events (6.5% vs. 3.9%; P=0.606). Kaplan-Meier analysis also showed a significantly higher rate of bleeding events in the combination therapy group, but no significant difference in the rate of embolic events. Inverse probability of treatment weighting revealed that combination therapy was independently associated with an increased risk of bleeding (hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.14–7.89, P=0.026), but not with the risk of embolic events (HR 0.30, 95% CI 0.04–2.59, P=0.275). Net clinical benefit analysis was almost negative for combination therapy vs. monotherapy.
Conclusions:In patients with AF and LAT, combination therapy was significantly associated with an increased risk of bleeding events, but not with a reduced risk of embolic events.