Comparison of Non-Gated vs. ECG-gated CT Angiography of Fontan Circulation in Patients with Implanted Stents in Pulmonary Branches.

BACKGROUND: Motion artifacts may degrade CT examination of Fontan pathway and hinder accurate diagnosis of in-stent restenosis. PURPOSE: We retrospectively compared ECG-gated multi-detector computed tomography (CT) with non-ECG-gated CT in order to demonstrate whether or not one of the methods should be preferred. METHOD: The study included 13 patients with surgically reconstructed Fontan pathway. A total of 16 CT examinations were performed between February 2010 and November 2015.The incidence of motion artifacts in Fontan pathway and pulmonary branches were analysed subjectively by two readers. The effective dose for each examination was calculated. RESULTS: Just in one non-gated CT examination was evidence of motion artifact in distal part of left pulmonary artery. The mean normalized effective radiation dose was 2.33 mSv (±0.62) for the non-ECG-gated scans and 4.55 mSv (±0.85) for the ECG-gated scans (p ≤ 0.05). CONCLUSION: Non-gated CT angiography with single phase reconstruction significantly reduces radiation dose without loss of image quality compared with ECG-gated CT angiography.

Pharmacomechanical thrombectomy for treatment of acute transplant renal artery thrombosis.

Acute transplant renal artery thrombosis is a rare complication in kidney transplantation that often leads to renal allograft loss. We present the first case of acute renal artery thrombosis 3 months after kidney transplantation, treated with pharmacomechanical thrombectomy with adjunctive catheter-directed thrombolysis and stent placement. The graft was salvaged with restoration of renal function and renal artery patency at the 3-year follow-up point.

Endovascular treatment of a giant aorto-ostial renal artery pseudoaneurysm.

Vascular complications after lumbar laminectomy are rare, but are potentially life-threatening. A 59-year-old man presented with progressive and worsening abdominal pain over several weeks. Multidetector computed tomography angiography revealed a large aorto-ostial left renal artery pseudoaneurysm 3 years after lumbar laminectomy. The pseudoaneurysm was successfully treated with a combination of various endovascular techniques ("jailed" microcatheter technique, stent-graft implantation, thrombin injection, balloon remodeling technique, Onyx application), with preserved patency of the left renal artery and pseudoaneurysm exclusion on 6-month follow-up multidetector computed tomography angiography. The size and location of this pseudoaneurysm and the combination of different techniques for endovascular treatment provides an update on current endovascular technology. Combination of different endovascular techniques can be a safe and feasible alternative for the treatment of complicated iatrogenic postlaminectomy vascular injuries and renal artery pseudoaneurysms.

Left internal mammary artery bypass dysfunction after revascularization of moderately narrowed coronary lesions. Colour-duplex ultrasound versus angiography study.

BACKGROUND: The left internal mammary artery (LIMA) is the conduit of choice for revascularization of coronary arteries and its popularity further increases in the era of mini-invasive coronary surgery. The aim of this study was first, to assess the accuracy of CDUS in predicting the LIMA graft dysfunction as compared to angiography, and secondly, to correlate the postoperative status of the LIMA graft with preoperative coronary artery stenosis severity of the bridged lesion. METHODS AND RESULTS: We examined 111 patients (pts) by colour-duplex ultrasound after myocardial revascularization by LIMA bypass (3.8 +/- 3.2 years after revascularization). LIMA was detected from the left supraclavicular approach at rest using the 7.5 MHz linear transducer. The ultrasound results were compared to contemporaneous angiography. The LIMA bypass patency was correlated with the preoperative coronary artery stenosis severity. The LIMA was detected by ultrasound in 92.8% (103) pts. At angiography, LIMA was patent and functional in 85 pts (76.6%, group A); in 25 subjects LIMA was stenosed or dysfunctional (22.5%, group B). In one patient the coronary subclavian steal syndrome was detected (0.9%). Haemodynamically moderate stenosis (50-60% by preoperative quantitative coronary angiography) was grafted in 5 pts of group A (6%), but in 10 pts of group B (40%) (P < 0.0001 vs group A). A peak systolic to peak diastolic velocity ratio (SDVR) of <2.0 yielded optimal accuracy to detect the absence of LIMA bypass dysfunction with a negative predictive value of 95%. CONCLUSION: 1. Revascularization of angiographically moderate coronary lesions is associated with a higher risk of postoperative graft dysfunction. 2. Colour-duplex ultrasound is a useful non-invasive tool for the postoperative follow-up of pts with a LIMA graft.

Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous mononuclear stem cell application for critical limb ischemia.

BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, acts as an inhibitor of angiogenesis and is associated with an increased risk of cardiovascular mortality. Administration of stem cells may affect endogenous mechanisms that regulate ADMA production and metabolism. The aim of the present study was to analyze ADMA concentration and changes in oxidative stress in patients with advanced critical limb ischemia (CLI) after bone marrow-derived mononuclear cell (BM-MNC) therapy. METHODS: Fifty patients (age 64 ± 11 years, 44 males, 6 females) with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were treated by intramuscular (n = 25) or intra-arterial (n = 25) injection of 40 ml BM-MNC concentrate. Patients with limb salvage and improved wound healing after 6 months were considered responders to cell therapy. The concentrations of markers of oxidative stress and angiogenesis were analyzed before, and at 3 and 6 months after BM-MNC delivery. RESULTS: At 6-month follow-up, four patients died of reasons unrelated to stem cell therapy. Among the survivors, 80% (37/46) showed limb salvage and improved wound healing. At 6 months follow-up, ADMA concentration significantly decreased in patients with limb salvage (1.74 ± 0.66 to 0.90 ± 0.49 µmol/L, p < 0.001), in parallel with decreased tumor necrosis factor (TNF)-α (2.22 ± 0.16 to 1.94 ± 0.38 pg/ml, p < 0.001), and increased reduced glutathione (6.96 ± 3.1 to 8.67 ± 4.2 µmol/L, p = 0.02), superoxide dismutase activity (168 ± 50 to 218 ± 37 U/L, p = 0.002), and coenzyme Q10 concentration (468 ± 182 to 598 ± 283 µg/L, p = 0.02). The number of delivered BM-MNCs significantly correlated with the decrease in ADMA concentration at 3 months (p = 0.004, r = -0.48) and the decrease in TNF-α concentration at 6 months (p = 0.03, r = -0.44) after cell delivery. ADMA or TNF-α improvement did not correlate with the number of applied CD34+ cells, C-reactive protein concentration, leukocyte count, or the dose of atorvastatin. CONCLUSIONS: The therapeutic benefit of BM-MNC therapy is associated with reduced ADMA levels and oxidative stress. Regulation of the ADMA-nitric oxide axis and improved antioxidant status may be involved in the beneficial effects of stem cell therapy. TRIAL REGISTRATION: The study was approved and retrospectively registered by ISRCTN registry, ISRCTN16096154 . Registered on 26 July 2016.

Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia.

BACKGROUND: The present study investigated factors associated with therapeutic benefits after autologous bone marrow cell (BMC) therapy in patients with "no-option" critical limb ischemia (CLI). METHODS AND RESULTS: Sixty-two patients with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were randomized to treatment with 40 ml of autologous BMCs (SmartPreP2) by local intramuscular (n = 32) or intra-arterial (n = 30) application. The primary endpoint was limb salvage and wound healing at 12 months. Seven patients (11 %) died during the follow-up from reasons unrelated to stem cell therapy. The BMC product of patients with limb salvage and wound healing (33/55) was characterized by a higher CD34(+) cell count (p = 0.001), as well as a higher number of total bone marrow mononuclear cells (BM-MNCs) (p = 0.032), than that of nonresponders (22/55). Patients with limb salvage and wound healing were younger (p = 0.028), had lower C-reactive protein levels (p = 0.038), and had higher transcutaneous oxygen pressure (tcpO2) (p = 0.003) before cell application than nonresponders. All patients with major tissue loss at baseline (Rutherford 6 stage of CLI, n = 5) showed progression of limb ischemia and required major limb amputation. In the multiple binary logistic regression model, the number of applied CD34(+) cells (p = 0.046) and baseline tcpO2 (p = 0.031) were independent predictors of limb salvage and wound healing. The number of administrated BM-MNCs strongly correlated with decreased peripheral leukocyte count after 6 months in surviving patients with limb salvage (p = 0.0008). CONCLUSION: Patients who benefited from autologous BMC therapy for "no-option" CLI were treated with high doses of CD34(+) cells. The absolute number of applied BM-MNCs correlated with the improvement of inflammation. We hypothesize that the therapeutic benefit of cell therapy for peripheral artery disease is the result of synergistic effects mediated by a mixture of active cells with regenerative potential. Patients at the most advanced stage of CLI do not appear to be suitable candidates for cell therapy. TRIAL REGISTRATION: The study was approved and registered by the ISRCTN registry. TRIAL REGISTRATION: ISRCTN16096154 . Registered: 26 July 2016.

Frequency of abdominal aortic aneurysm in patients >60 years of age with coronary artery disease.

Using B-mode ultrasound, we studied the prevalence of abdominal aortic aneurysm (AAA; diameter > or =3 cm) and its predictive risk factors in 109 consecutive patients who were >60 years of age and had coronary artery disease (CAD). A group of 60 age-matched patients who did not have CAD served as controls. The prevalence of AAA was higher in the CAD group than in the control group (14%, 16 of 109, vs 3%, 2 of 60, p <0.05). By multivariate analysis, only smoking was strongly associated with AAA (odds ratio 4.86, 95% confidence interval 1.55 to 15.25). In contrast, presence of diabetes mellitus was negatively associated with AAA in univariate analysis (odds ratio 0.11, 95% confidence interval 0.01 to 0.83) and a strong trend of inverse association remained in multivariate analysis (odds ratio 0.12, 95% confidence interval 0.01 to 1.03). Thus, systematic screening can detect AAA in 1 of 7 patients who are >60 years of age and have CAD. AAA shares some, but not all, risk factors of atherosclerosis.

Intra-arterial autologous bone marrow cell transplantation in a patient with upper-extremity critical limb ischemia.

Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

Characterization of mesenchymal stem cells of "no-options" patients with critical limb ischemia treated by autologous bone marrow mononuclear cells.

BACKGROUND: Application of autologous bone marrow mononuclear cells to "no option" patients with advanced critical limb ischemia (CLI) prevented major limb amputation in 73% patients during the 6-month follow-up. We examined which properties of bone marrow stromal cells also known as bone-marrow derived mesenchymal stem cells of responding and non-responding patients are important for amputation-free survival. METHODS AND FINDINGS: Mesenchymal stem cells of 41 patients with CLI unsuitable for revascularisation were isolated from mononuclear bone marrow concentrate used for their treatment. Based on the clinical outcome of the treatment, we divided patients into two groups: responders and non-responders. Biological properties of responders' and non-responders' mesenchymal stem cells were characterized according to their ability to multiply, to differentiate in vitro, quantitative expression of cell surface markers, secretion of 27 cytokines, chemokines and growth factors, and to the relative expression of 15 mesenchymal stem cells important genes. Secretome comparison between responders (n=27) and non-responders (n=14) revealed significantly higher secretion values of IL-4, IL-6 and MIP-1b in the group of responders. The expression of cell markers CD44 and CD90 in mesenchymal stem cells from responders was significantly higher compared to non-responders (p<0.01). The expression of mesenchymal stem cells surface markers that was analyzed in 22 patients did not differ between diabetic (n=13) and non-diabetic (n=9) patient groups. Statistically significant higher expression of E-cadherin and PDX-1/IPF1 genes was found in non-responders, while expression of Snail was higher in responders. CONCLUSIONS: The quality of mesenchymal stem cells shown in the expression of cell surface markers, secreted factors and stem cell genes plays an important role in therapeutic outcome. Paracrine mechanisms are main drivers in the induction of reparatory processes in CLI patients. Differences in mesenchymal stem cells properties are discussed in relation to their involvement in the reparatory process.

No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia.

Stem cell therapy has been proposed to be an alternative therapy in patients with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization. We compared the therapeutic effects of intramuscular (IM) and intra-arterial (IA) delivery of bone marrow cells (BMCs) and investigated the factors associated with therapeutic benefits. Forty-one patients (mean age, 66 ± 10 years; 35 males) with advanced CLI (Rutherford category, 5 and 6) not eligible for revascularization were randomized to treatment with 40 ml BMCs using local IM (n = 21) or selective IA infusion (n = 20). Primary endpoints were limb salvage and wound healing. Secondary endpoints were changes in transcutaneous oxygen pressure (tcpO(2)), quality-of-life questionnaire (EQ5D), ankle-brachial index (ABI), and pain scale (0-10). Patients with limb salvage and wound healing were considered to be responders to BMC therapy. At 6-month follow-up, overall limb salvage was 73% (27/37) and 10 subjects underwent major amputation. Four patients died unrelated to stem cell therapy. There was significant improvement in tcpO(2) (15 ± 10 to 29 ± 13 mmHg, p < 0.001), pain scale (4.4 ± 2.6 to 0.9 ± 1.4, p < 0.001), and EQ5D (51 ± 15 to 70 ± 13, p < 0.001) and a significant decrease in the Rutherford category of CLI (5.0 ± 0.2 to 4.3 ± 1.6, p < 0.01). There were no differences among functional parameters in patients undergoing IM versus IA delivery. Responders (n = 27) were characterized by higher CD34(+) cell counts in the bone marrow concentrate (CD34(+) 29 ± 15×10(6) vs. 17 ± 12×10(6), p < 0.05) despite a similar number of total nucleated cells (4.3 ± 1.4×10(9) vs. 4.1 ± 1.2×10(9), p = 0.66) and by a lower level of C-reactive protein (18 ± 28 vs. 100 ± 96 mg/L, p < 0.05) as well as serum leukocytes (8.3 ± 2.1×10(9)/L vs. 12.3 ± 4.5×10(9)/L, p < 0.05) as compared with nonresponders (10 patients). Both IM and IA delivery of autologous stem cells are effective therapeutic strategies in patients with CLI. A higher concentration of CD34(+) cells and a lower degree of inflammation are associated with better clinical therapeutic responses.

Endovascular treatment of late in-stent-graft dissection after thoracic endovascular aneurysm repair.

Complications after endovascular repair of thoracic aortic pathologies may be devastating. We report the case of endovascular treatment of late in-stent-graft dissection after thoracic endovascular aneurysm repair (TEVAR). A 25-year-old man was admitted to our hospital 2 years after endovascular treatment of posttraumatic aortic pseudoaneurysm using stent-graft implantation with an acute sudden onset of ischemia in both legs with absent femoral pulses, numbness, and renal functions deterioration. Multidetector computed tomography (MDCT) angiography showed an intimal flap in the distal part of the stent-graft with critical stenosis of the residual lumen. The patient was successfully treated with stent-graft implantation by way of percutaneous approach while under local anesthesia. The risk of this late complication after TEVAR should be considered during follow-up, especially in young patients with increased physical activity. Endovascular treatment can be the method of choice for these patients.

The recurrence of iatrogenic femoral artery pseudoaneurysm after occlusion by ultrasound guided percutaneous thrombin injection.

AIMS: To evaluate efficacy of percutaneous ultrasound-guided thrombin injection (UGTI) of iatrogenic femoral artery pseudoaneurysm (PSA) and to identify the risk factors associated with PSA recurrence. METHODS AND RESULTS: We treated 140 patients aged 76 years (range 49-83) presented with femoral artery PSA after cardiac catheterisation by percutaneous UGTI (500 IU/ml solution of activated human thrombin). Factors associated with the recurrence of PSA were analysed. One hundred nineteen patients were successfully treated by one injection of thrombin (immediate success rate 85%). In 19 patients (13.6%), short local compression following injection was needed for complete occlusion (overall success rate 98.6%, 138/140). In one case, progression of PSA required conversion to surgery (0.7%). In one patient with pre-existing stenosis of superficial femoral artery, acute limb ischaemia developed after UGTI (0.7%). The recurrence of PSA in 30-days follow-up (10 patients, 7%) was associated with obesity (BMI>30, OR=1.39, 95% CI 1.09-1.78, p<0.05), and with extensive combination of anti-aggregation and anti-coagulation therapy (OR=2.11, 95% CI 1.23-3.62, p<0.0001) as revealed by both univariate and multivariate analysis. CONCLUSIONS: The UGTI is a safe and effective treatment of iatrogenic femoral artery PSA. Recurrence is low and associated with obesity and extensive use of combined anti-aggregation and anti-coagulation therapy.