Adenovirus-mediated gene transfer to lower limb artery of patients with chronic critical leg ischemia.

Arterial gene transfer offers a promising new approach for the treatment of vascular disorders. However, no data are available about the gene transfer efficiency in human arteries in vivo. The aim of this study was to evaluate the safety and feasibility of catheter-mediated adenoviral gene transfer in human peripheral arteries. Ten patients (8 females, 2 males, mean age 80 +/- 8 years) suffering from chronic critical leg ischemia with a prior decision for amputation were recruited in the study. Gene transfer was performed in eight patients in conjunction with a conventional percutaneous transluminal angioplasty, using a perfusion coil balloon catheter. Two patients served as controls. Increasing concentrations of replication-deficient adenoviruses (titers from 1 x 10(8) to 4 x 10(10) PFU) containing a nuclear-targeted beta-galactosidase marker gene were administered into the arteries over 10 min via the catheter. Amputations were performed 20 to 51 hr after the procedures and gene transfer efficiency was evaluated in the transduced arteries using X-Gal staining for beta-galactosidase activity. Beta-galactosidase gene transfer was well tolerated and no adverse tissue responses or systemic complications were observed in any of the patients. Gene transfer was successful in six of the eight patients. Gene transfer efficiency varied between 0.04 and 5.0% of all arterial cells. Transgene expression was detected in smooth muscle cells, endothelial cells, and macrophages and in tunica adventitia. However, transgene activity was not evenly distributed in the arterial wall and no transgene activity was found beneath advanced atherosclerotic lesions. The safety and feasibility of in vivo gene transfer by adenoviral vectors to human peripheral arteries were established. Although improvements are still required in gene transfer efficiency, these findings suggest that adenoviruses can be used to deliver therapeutically active genes into human arteries.

Angiographic predictors of graft patency and disease progression after coronary artery bypass grafting with arterial and venous grafts.

BACKGROUND: There are few data about angiographic determinants of functional graft patency and native artery disease progression after coronary artery bypass grafting operation with arterial grafts compared with venous grafts. METHODS: Baseline and follow-up coronary angiograms at a mean of 2 years after operation in 91 patients with 194 arterial and 204 venous graft anastomoses were analyzed. RESULTS: Ninety-two percent of the arterial and 87% of the venous graft anastomoses were patent at follow-up angiography (p = 0.05, odds ratio = 2.63). Unlike that of arterial grafts, the patency rate of venous graft anastomoses correlated negatively with decreasing severity of the bypassed lesion. In contrast to venous grafts, in which angiographic graft function was basically dichotomous (fully patent or occluded), compromised flow of the arterial graft anastomoses was registered in 12%. Progression of the disease was more common in segments bypassed with venous grafts than with arterial grafts (p = 0.001, odds ratio = 2.03). CONCLUSIONS: Angiographic determinants of functional graft patency and progression of occlusive changes in the bypassed artery segments are different for arterial and venous grafts.

Dissecting aneurysms of all four cervicocranial arteries in fibromuscular dysplasia: treatment with self-expanding endovascular stents, coil embolization, and surgical ligation.

A patient with cervicocranial fibromuscular dysplasia (FMD) presented with subarachnoid hemorrhage. A ruptured dissecting distal vertebral artery aneurysm required clip ligation of the parent artery; a contralateral dissecting proximal vertebral aneurysm was occluded with detachable coils. Progressive dissecting, extracranial aneurysms of the internal carotid artery were treated with self-expanding stents. Subsequent angiography and intravascular sonography revealed patent stents, a smooth luminal surface, and total occlusion of the aneurysm. Clinical outcome was excellent.

Percutaneous endovascular stenting: development, investigation and application.

Percutaneous endovascular stenting (PES), a new and alternative approach of interventional radiologic techniques, has encouraging potentials for management of vascular obstructive diseases. The most important role of PES is to prevent the risk of abrupt closure and to reduce the rate of early and late post-angioplasty restenosis (PARS) of PTA. Because of different working mechanisms, various stents show different advantages and disadvantages. Specific indications of PES are: (1) further compensation for failed PTA, (2) management of complications due to PTA and (3) primary treatment of vascular obstructive diseases. Based on a preliminary comparison with atherectomy, laser angioplasty and PTA, PES seems to provide an advantage for long-term patency of large caliber vessels such as iliac arteries, while more significant problems still exist in PES with small caliber vessels such as femoral-popliteal and coronary arteries. Further comparative clinical research is required to establish the utility of PES among other intraluminal techniques of vascular interventions.

Image processing in digital chest radiography: effect on diagnostic efficacy.

The usefulness of digital image processing of chest radiographs was evaluated in a clinical study. In 54 patients, chest radiographs in the posteroanterior projection were obtained by both 14 inch digital image intensifier equipment and the conventional screen-film technique. The digital radiographs (512 x 512 image format) viewed on a 625 line monitor were processed in three different ways: (1) standard display; (2) digital edge enhancement for the standard display; and (3) inverse intensity display. The radiographs were interpreted independently by three radiologists. The diagnoses were confirmed by CT, follow-up radiographs and clinical records. Chest abnormalities of the films analyzed included 21 primary lung tumors, 44 pulmonary nodules, 16 cases with mediastinal disease and 17 cases with pneumonia/atelectasis. Interstitial lung disease, pleural plaques, and pulmonary emphysema were found in 30, 18 and 19 cases, respectively. The sensitivity of conventional radiography when averaged overall findings was better than that of the digital techniques (P less than 0.001). The differences in diagnostic accuracy measured by sensitivity and specificity between the three digital display modes were small. Standard image display showed better sensitivity for pulmonary nodules (0.74 vs 0.66; P less than 0.05) but poorer specificity for pulmonary emphysema (0.85 vs. 0.93; P less than 0.05) compared with inverse intensity display. We conclude that when using 512 x 512 image format, the routine use of digital edge enhancement and tone reversal at digital chest radiographs is not warranted.

Impact of risk factors on limb salvage after angioplasty in chronic critical lower limb ischemia. A prospective trial.

The impact of various general risk factors on long-term results of percutaneous transluminal angioplasty (PTA) in chronic critical lower limb ischemia is poorly known. In a prospective trial 209 PTAs were performed in 103 consecutive patients with 117 limbs with chronic critical ischemia. The general risk factors that might affect the long-term results of PTA in this patient population were reviewed. Among the factors that showed no statistical significance were all associated diseases, smoking history, and medication used. Of the various clinical chemical parameters, only serum high density lipoprotein (S-HDL) cholesterol and plasma fibrinogen had a statistically significant influence on limb salvage rate in Kaplan-Meier analysis. These parameters proved to be significant determinants also in Cox multiple regression analysis when PTA target-vessel-related parameters (peripheral runoff and number of diseased vessels) were also included in the model. Cox model predicts up to 86% one-year limb salvage for the "good" group (one to five diseased lower limb vessels/limb, S-HDL cholesterol > 0.78 mmol/L, plasma fibrinogen < 4.9 g/L).

Percutaneous transluminal angioplasty in critical limb ischaemia.

To determine the utility of percutaneous transluminal angioplasty (PTA) in the treatment of chronic critical lower-limb ischaemia, a prospective study of 103 consecutive patients (117 limbs) was performed. A total of 209 lesions were treated in the iliac (n = 4), femoropopliteal (n = 121), and intrapopliteal (n = 84) arteries. The follow-up time was 1-36 months (mean 12 months). The technical success rate was 92% for stenosis and 80% for occlusion. The cumulative limb salvage rate was 56% at one year, 49% at two years and 49% at three years. The following factors correlated favourably with limb salvage in Cox multiple regression analyses: a small number of diseased lower-limb vessels (one to five vs six to eight) and treated lesions per limb (one to two vs three to five), peripheral runoff after PTA (at least one patent calf vessel vs none) and an occlusion as the successfully treated lesion (instead of stenosis).

Impact of different patency criteria on long-term results of femoropopliteal angioplasty: analysis of 106 consecutive patients with claudication.

PURPOSE: To assess the impact of different patency criteria on long-term results after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. PATIENTS AND METHODS: The results of femoropopliteal PTA in 106 consecutive patients with claudication (140 treated limbs) were analyzed. The treated artery segment was considered patent if (a) the ankle-brachial index (ABI) had increased by more than 0.10 initially and not deteriorated by more than 0.15 from the maximum early postprocedural level and (b) the ABI was consistently at least 0.15 above the preprocedural level. The third criteria was based on patients' subjective assessment of patency. Initial failures were either included or excluded and both primary (the outcome of the original PTA) and secondary patency (also repeated PTAs included) were determined. RESULTS: When the different criteria were applied, the patency rates at 3 years ranged from 42% to 82% in this patient population. CONCLUSION: These results stress the importance of uniform criteria when results of different kind of vascular interventions are reported.

Complications of lower-limb percutaneous transluminal angioplasty: a prospective analysis of 410 procedures on 295 consecutive patients.

PURPOSE: To evaluate complications and their predictors in percutaneous transluminal angioplasty (PTA) of lower-limb arteries. METHODS: Complications in 410 angioplasty procedures in 295 consecutive patients (192 claudicants and 103 suffering from chronic critical ischemia) were prospectively analyzed. RESULTS: The total complication rate was 10.5% (43/410). There were 21 major complications (5%), eight of which required surgical treatment, including four hematomas, two arteriovenous fistulae, and two pseudoaneurysms at the puncture site, two retroperitoneal hematomas, and 11 thrombotic/thromboembolic complications. There were significantly more complications with treatment of occlusions compared with stenoses (18% vs 7%, p = 0.002). Women had significantly more bleeding complications than men (15% vs 6%, p = 0.032). The 30-day mortality rate in patients with critical ischemia was 10%. CONCLUSION: In lower-limb PTA a few target lesion- and patient-related determinants of complications could be identified. In patients with critical ischemia, the 30-day mortality was rather high and mainly due to associated coronary and cerebrovascular diseases.

Angiographic characteristics of symptomatic recurrent disease after infrainguinal percutaneous transluminal angioplasty.

PURPOSE: To evaluate the angiographic patterns of clinically manifest recurrent disease after infrainguinal percutaneous transluminal angioplasty (PTA) of stenoses and total occlusions. METHODS: Among 326 infrainguinal PTAs on 263 consecutive patients, selective angiography was performed on 61 limbs of 52 patients 1-60 months after the primary intervention because of clinically suspected recurrent disease. Lesion-specific and patient-related factors were analyzed for 75 angiographically confirmed recurrent lesions in 57 limbs of 48 patients. RESULTS: Recurrent disease was more frequently a stenosis when the original target lesion was a stenosis (92%, 44/48) than when the original lesion was a total occlusion (59%, 16/27; p < 0.001). When the original target lesion was a stenosis, the total length of the recurrent disease was longer than that of the original lesion [3.9 +/- 3.9 cm (mean +/- standard deviation) vs 2.8 +/- 2.7 cm; p = 0.03], while in the subgroup of original total occlusions the length of the recurrent lesion was shorter than that of the original occlusion (7.1 +/- 5.0 cm vs 9.9 +/- 6.9 cm; p = 0.02). Half the restenosis (22/44) extended beyond one or both ends of the original stenosis and 38% (6/16) of the reocclusions extended beyond the distal end of the original occlusion. CONCLUSIONS: The type of recurrent disease depends on the original lesion type and the restenotic lesion frequently extends beyond one or both ends of the original target lesion.

Brachial artery access for percutaneous renal artery interventions.

PURPOSE: To evaluate the suitability of transbrachial access for endovascular renal artery interventions. METHODS: During 37 consecutive endovascular renal artery interventions, the transbrachial approach was used on nine patients (mean age 63 years; range 41-76 years) for 11 renal artery procedures on native kidneys and one percutaneous transluminal angioplasty (PTA) on a transplanted kidney. The reason for using transbrachial access was a steep aorta-renal angle in five, and severe aorta-iliac atherosclerosis in the remaining patients. In addition to the intervention catheter in the left brachial artery, an additional nonselective catheter for controlling the procedure was inserted transfemorally (six patients) or via the contralateral brachial artery. RESULTS: Eleven interventions (six PTAs, five stents) were successfully completed. The one failure resulted from impenetrable subclavian artery stenosis. The only major complication was a brachial artery pseudoaneurysm requiring surgical treatment. CONCLUSION: Transbrachial access is an effective and relatively safe technique for renal artery interventions when transfemoral access is not possible.

Chronic critical lower-limb ischemia: prospective trial of angioplasty with 1-36 months follow-up.

To determine the utility of percutaneous transluminal angioplasty (PTA) in the treatment of chronic critical lower-limb ischemia, a prospective study of 103 consecutive patients (117 limbs) was performed. Patients underwent PTA for a total of 209 lesions in the iliac (n = 4), femoropopliteal (n = 121), and infrapopliteal (n = 84) arteries and were followed up for 1-36 months (mean, 12 months). The primary technical success rate was 92% for stenosis and 80% for occlusion. Survival analysis with the Kaplan-Meier method revealed 1-, 2-, and 3-year limb salvage rates of 56%, 49%, and 49%, respectively. The following factors correlated favorably with limb salvage in Cox multiple regression analyses: a small number of diseased lower-limb vessels (one to five vs six to eight) and treated lesions per limb (one or two vs three to five), achieved peripheral runoff (one to three patent calf vessels vs none), and an occlusion as the successfully treated target lesion (instead of stenosis).

Percutaneous transluminal angioplasty in femoral artery occlusions: primary and long-term results in 107 claudicant patients using femoral and popliteal catheterization techniques.

To assess the impact of percutaneous transluminal angioplasty (PTA) of occluded femoral arteries, a prospective study of 107 claudicant patients was performed. A total of 117 limbs were treated and were followed for 1-36 months; the mean length of treated occlusions was 7.4 cm (range 2-25 cm). Eighty-nine recanalizations were performed using antegrade femoral and 28 using the retrograde popliteal catheterization technique. With logistic regression a short length of occlusion correlated favourably with early success. Including rePTAs and applying standardized criteria, survival analysis with the Kaplan-Meier method revealed a 3-year secondary patency rate of 55% for all the treated limbs. The following factors had negative influence on primary patency after successful recanalization; presence of soft thrombotic material in the recanalized artery segment and the presence of focal dissections after PTA. In univariate and multiple logistic regression analysis, male gender and a lesser extent of the atherosclerotic disease (assessed by the number of diseased vessels in the treated limb) correlated with a lower frequency of PTA procedure complications. There was no statistically significant difference in the complications, in the primary success or in the long-term results using either the femoral or popliteal route. However, the popliteal approach improved the early success of the originally antegrade access group by 6% and increased by about one-fifth the number of patients considered technically feasible for PTA in femoral artery occlusions. PTA can be used in femoral artery occlusions up to 10 cm long and it is especially suitable in femoral artery occlusions not exceeding 5 cm in length. PTA can be tried in femoral artery occlusions exceeding a length of 10 cm if operative treatment is not suitable.

Brachial arterial access: endovascular treatment of failing Brescia-Cimino hemodialysis fistulas--initial success and long-term results.

PURPOSE: To evaluate safety and efficacy of endovascular interventions in failing antebrachial Brescia-Cimino hemodialysis fistulas in consecutive patients. MATERIALS AND METHODS: Altogether, 103 interventions were performed in 53 Brescia-Cimino shunts in 51 patients by means of antegrade brachial arterial access. Twelve interventions were initiated with pharmacomechanical thrombolysis and/or thromboaspiration. All interventions included balloon angioplasty that was completed with stent placement in eight cases and with endovascular brachytherapy with an iridium 192 source in five cases. RESULTS: The technical success rate of the primary interventions was 92% (49 of 53) and that for all interventions was 95% (98 of 103). The rate of major complications was 4% (four of 103). Clinical success was achieved in 92% (95 of 103) of the interventions. By including the initial failures, 58% +/- 7 (standard error of the estimate), 44% +/- 8, 40% +/- 8, and 32% +/- 10 primary and 90% +/- 5, 85% +/- 5, 79% +/- 7, and 79% +/- 7 secondary clinical patency rates were registered at 6 months and 1, 2, and 3 years, respectively, by means of Kaplan-Meier analysis. The location of the main treated lesion at the arteriovenous anastomosis (P =.03) was a predictor of poorer long-term patency. CONCLUSION: Endovascular interventions with antegrade brachial arterial access are highly effective in restoring function in failing Brescia-Cimino fistulas.

Comparison of iodixanol 270 with iohexol 300 in infrapopliteal arteriography. Digital densitometric analysis of angiographic opacification.

PURPOSE: To compare iodixanol 270 mg I/ml with iohexol 300 mg I/ml in infrapopliteal arteriography by measuring digital densitometric vessel opacification and by visually assessing angiographic enhancement. MATERIAL AND METHODS: In a double-blind, dual-balanced, 4-sequence cross-over design, 50 claudicant patients received two contrast media injections (10 min interval) in the superficial femoral artery. Digital angiography was performed at 8 frames/s and time-density curves with a circular region of interest over a distal calf artery were generated. A mixed, linear model was used to identify effects influencing the density measurements. Subjective evaluation of the image quality was made independently by two observers. RESULTS: No statistically significant difference between the contrast media was revealed in the analysis of the densitometric measurements (p=0.14) nor in the subjective visual evaluation (p=0.74). However, the mean density at the time of maximum opacification was higher after the first injection than that after the second injection (p=0.02). There was a tendency towards lower intensity of warmth during injection of iodixanol 270 than during injection of iohexol 300. CONCLUSION: In patients with severe occlusive atherosclerotic disease, iodixanol yielded the same image quality as iohexol in infrapopliteal arteriography, in spite of the 30 mg I/ml lower iodine concentration.

Prospective trial of infrapopliteal artery balloon angioplasty for critical limb ischemia: angiographic and clinical results.

PURPOSE: To evaluate the safety and efficacy of infrapopliteal percutaneous transluminal angioplasty (PTA) as a primary treatment of chronic critical limb ischemia in a prospective trial. MATERIALS AND METHODS: Infrapopliteal PTA was performed on 72 limbs of 60 patients (mean age, 72 y; range, 38-92 y) and patients were followed for 12-24 months. RESULTS: The primary angiographic success rate for the stenoses was 84% (102 of 121) and that for the occlusions was 61% (41 of 67) with corresponding restenosis rates of 32% and 52% at follow-up angiography performed a mean of 10 months after primary PTA. The rate of major complications was 2.8% (access site pseudoaneurysms in two patients). The primary clinical success was 63% (45 of 72). A 48% cumulative primary patency rate, a 56% secondary patency rate, and a 80% cumulative limb salvage rate were registered at 18 months, as determined with use of Kaplan-Meier analysis. Lack of angiographic improvement at the site of the most severe ischemia and renal insufficiency (serum creatinine level > 130 micromol/L) were independent predictors of poorer long-term clinical results, as determined with use of Cox multiple regression analysis. CONCLUSIONS: Infrapopliteal PTA is a feasible primary treatment of chronic critical limb ischemia with moderate primary angiographic and clinical success, a low complication rate, and a cumulative limb salvage rate comparable with surgical techniques.