Real-world outcomes of endovascular treatment in a non-selected population with peripheral artery disease - prospective study with 2-year follow-up.

Background: The study aimed to evaluate the outcomes of percutaneous transluminal angioplasty (PTA) in lower-extremity peripheral artery disease (PAD) patients. Patients and methods: A multi-centre, observational study was performed with 32 German and Austrian centres contributing data to the PTA registry. Data of 1,781 patients with lower-leg and pelvic PAD who were suitable for endovascular PTA treatment were contributed from participating centres. Data from 1,533 patients are reported here (1,055 male and 478 female). This study did not have exclusion criteria. Quality of life (QOL) questionnaire (EQ-5D) scores, Rutherford classification, mortality, patency rate and details of major adverse cardiovascular events were collected at 6-, 12-, 18-, and 24-month follow ups. Results: PTA with/without stenting achieved 90.3 %, 86.5 %, 82.7 %, and 71.9 % technical success (recanalisation achieving ≥ 70 % patency, no evidence of embolisation, recoiling or dissection) in iliac, femoral, popliteal, and below-the-knee arteries, respectively. Procedural/postprocedural complications occurred in 142 (9.3 %, 1 death) and 74 (4.8 %) patients. QOL, mobility, self-care, activity, and pain/discomfort scores improved (p < 0.01), anxiety/depression was insignificantly improved. During follow-up, 409 (26.7 %) patients were hospitalised for PAD, 281 (18.3 %) required reintervention, and 145 (9.5 %) died or needed amputation (n = 49; 3.2 %). Multivariate analysis demonstrated poorer outcomes in patients with comorbidities. Conclusions: PTA with/without stenting is effective, safe, and widely applicable, with few complications. It improves QOL, but not anxiety/depression.

Credentialing in interventional therapy in Europe - comparison of curricula including endovascular therapy of arterial diseases.

The prevalence of peripheral artery disease (PAD) is continuously increasing. In addition, the treatment of PAD has changed substantially over the last decades. Novel treatment modalities and diagnostic tools were developed and endovascular therapy was established as a first-line therapy. In consequence, vascular medicine has become an interdisciplinary field, involving different specialties such as internal medicine/cardiology, internal medicine/angiology, vascular surgery, and (interventional) radiology. Attributed to the expanding field and to ensure high quality and standardized training, various curricula were developed. Not only within the different medical disciplines but across countries. We compared the training programmes in Germany, Switzerland, and Europe and found a great variety in these curricula and programmes. Nevertheless, we identified first attempts to harmonize training requirements within the various societies: the interdisciplinary guidelines of the German Society for Cardiology (DGK) and the German Society of Angiology, the adoption of European standards on a national level, and the Swiss initiative of the Union of Vascular Societies of Switzerland (UVSS). The standard and level of training is high in all curricula and societies. However, further harmonization is needed to optimize patient care and ensure a uniform quality level across different vascular societies.

Paclitaxel-releasing balloon in femoropopliteal lesions using a BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial.

PURPOSE: To evaluate the safety and efficacy of the novel Passeo-18 Lux paclitaxel-coated balloon compared with the Passeo-18 uncoated balloon in patients with symptomatic de novo or restenotic femoropopliteal lesions. METHODS: Sixty patients (34 men; mean age 70.7 ± 10.1 years) in 5 European centers were enrolled in the BIOLUX P-I trial (ClinicalTrials.gov identifier NCT01056120) and randomized 1:1 to either the paclitaxel-coated balloon or the uncoated balloon. The primary endpoint was late lumen loss at 6 months. Secondary endpoints were binary restenosis at 6 months, clinically driven target lesion revascularization (TLR), change in ankle-brachial index and Rutherford classification, and major adverse events at 6 and 12 months. RESULTS: At 6 months, patients treated with paclitaxel-coated balloons had a significantly lower late lumen loss (0.51 ± 0.72 vs. 1.04 ± 1.00 mm, p = 0.033) and binary restenosis (11.5% vs. 34.6%, p = 0.048) than the control group. Correspondingly, clinically driven TLR was lower in the paclitaxel-coated balloon group at 12 months [15.4% vs. 41.7% (p = 0.064) for the intention-to-treat population and 16.0% vs. 52.9%, (p = 0.020) for the as-treated population]. No death and one minor amputation were observed compared with two deaths and two minor amputations in the control group. No major amputations or thrombosis were reported. CONCLUSION: The Passeo-18 Lux paclitaxel-coated balloon has been proven to be safe and effective in patients with femoropopliteal lesions, with superior performance outcomes compared with treatment with an uncoated balloon.

Primary Self-EXPANDing Nitinol Stenting vs Balloon Angioplasty With Optional Bailout Stenting for the Treatment of Infrapopliteal Artery Disease in Patients With Severe Intermittent Claudication or Critical Limb Ischemia (EXPAND Study).

PURPOSE: To compare primary placement of a self-expanding nitinol stent to percutaneous transluminal angioplasty (PTA) with bailout stenting in infrapopliteal arteries of patients with severe intermittent claudication or critical limb ischemia (CLI). METHODS: In the EXPAND trial (ClinicalTrials.gov; identifier NCT00906022), 92 patients (mean age 72.9±9.5 years; 62 men) undergoing treatment for infrapopliteal stenosis in 11 European centers were randomized 1:1 to either self-expanding nitinol stenting with the Astron Pulsar/Pulsar-18 nitinol stent or PTA with bailout stenting. The primary endpoint was sustainable clinical improvement after 12 months, defined as a ≥1-category increase for Rutherford category 3 patients or a ≥2-category increase for CLI patients (Rutherford categories 4/5) compared with baseline. Furthermore, target lesion revascularization (TLR), mortality, and amputation were assessed after 12 months. RESULTS: Sustained clinical improvement at 1 year was observed in 74.3% of the patients treated with primary stenting and in 68.6% of the patients treated with PTA and bailout stenting (p>0.05). Kaplan-Meier estimates of freedom from TLR (76.6% and 77.6%), mortality (7.4% vs 2.1%), and amputation [8.9% (major 6.7%) vs 13.2% (major 8.7%)] at 1 year were not significantly different. CONCLUSION: Primary self-expanding nitinol stenting did not show statistically different clinical outcomes compared to angioplasty with bailout stenting for infrapopliteal lesions.

Non-coronary atherosclerosis.

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.

German multicenter real-world registry of stenting for superficial femoral artery disease: clinical results and predictive factors for revascularization.

PURPOSE: To investigate nitinol stent treatment of superficial femoral artery (SFA) lesions and the impact of different risk factors on the need for clinically driven target lesion revascularization (TLR) in a large, real-world population of claudicants. METHODS: Patients presenting with symptomatic SFA stenosis >70% were consecutively enrolled in the 13-center MARIS prospective registry (ClinicalTrials.gov identifier NCT01067885). There was no restriction on lesion length, thus leading to the inclusion of a real-world as well as high-risk patient cohort. The 998 participating patients (657 men; mean age 67.4±9.2 years) had 1050 lesions treated with the same nitinol stent type. The mean lesion length was 9.5±9.6 cm (range 0.5-44; median 8.0); more than a third of the lesions (450, 42.9%) were total occlusions. The primary endpoint was the need for clinically driven target lesion revascularization (TLR) at 12 months. RESULTS: Acute technical success was achieved in 1042 (99.2%) lesions. Restenosis occurred in 187 (23.7%) and reocclusion in 79 (10.0%) lesions at 12 months. The primary endpoint of TLR at 12 months was reached by 136 (17.2%) patients. The periprocedural complication rate was 5.4%. Independent predictors of TLR were female gender [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.3 to 0.7, p<0.001] and lesion length >20 cm vs. 10 cm (OR 2.7, 95% CI 1.1 to 6.6, p=0.029) and 10-20 cm vs. 10 cm (OR 1.9, 95% CI 1.0 to 4.1, p=0.047). CONCLUSION: Stent implantation in the SFA is safe and associated with favorable acute and midterm results in a real-world setting. Lesion length and female gender were identified as independent risk factors for TLR.

MISAGO 2: one-year outcomes after implantation of the Misago self-expanding nitinol stent in the superficial femoral and popliteal arteries of 744 patients.

PURPOSE: To evaluate the safety and efficacy of the Misago self-expanding rapid-exchange nitinol stent system for the treatment of femoropopliteal occlusive disease in a prospective multicenter observational trial (ClinicalTrials.gov; identifier NCT01118117). METHODS: Between April and October 2008, the registry enrolled 744 patients (496 men; 69 ± 10 years) who had symptomatic ≥ 70% stenosis or occlusion of the superficial femoral or popliteal arteries treated with the Misago stent. Mean length of the 750 lesions was 63.9 mm; 282 (37.6%) vessels were completely occluded. Primary study endpoints were the need for target lesion revascularization (TLR) and event-free survival rates for the assessment of efficacy and safety, respectively. At 6 and 12 months post intervention, clinical symptoms of recurrent ischemia and/or claudication, Rutherford category, and ankle-brachial index (ABI) at rest were assessed. RESULTS: In the study period, 945 stents were successfully deployed in the 750 lesions. The overall TLR rate was 10.1% among 671 (90.3%) patients evaluated at 1 year [3.1% among 709 (95.3%) patients at 6 months]. Event-free survival at 12 months was 84.9%. Mean ABIs improved by ≥ 0.1 in three quarters of the patients (76.0%) over 12 months. The Rutherford grade improved or remained stable in the majority of patients (95.5%) after 1 year. Stent fractures (13 grade 1, 2 grade 2) in 3.1% of stents examined radiographically (n=484) at 1 year were not related to any clinical events. Primary patency was recorded in 574 (87.6%) patients evaluated at 1 year post procedure. CONCLUSION: The Misago rapid-exchange nitinol stent showed promising efficacy and safety results, with a low stent fracture rate, in patients with femoropopliteal disease, making it a safe and reliable treatment option.

Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST).

BACKGROUND: Endoluminal treatment of superficial femoral artery lesions is a matter of controversy. The present study was designed to investigate the impact of nitinol stenting of superficial femoral artery lesions with a maximum length of 10 cm on restenosis and clinical outcomes at 1 year. METHODS AND RESULTS: Two hundred forty-four patients (168 men; 66+/-9 years) with a single superficial femoral artery lesion and chronic limb ischemia were randomized to implantation of a single Bard Luminexx 3 stent (123 patients) or stand-alone percutaneous transluminal angioplasty (PTA) (121 patients). Mean lesion length was 45 mm. Technical success (residual stenosis <50% for PTA, <30% for stenting) was achieved in 96 patients assigned to PTA (79%) and 117 patients assigned to stenting (95%); 13 PTA group patients (11%) "crossed over" to stenting. At 1 year, the primary end point of ultrasound-assessed binary restenosis was reached in 39 of 101 PTA group patients (38.6%) and 32 of 101 stent group patients (31.7%; absolute treatment difference, -6.9%; 95% CI, -19.7% to 6.2%; P=0.377). Target lesion revascularization rates at 1 year were 18.3% and 14.9%, respectively (absolute treatment difference, -3.3%; 95% CI, -13.0% to 6.4%; P=0.595). No statistically significant difference between treatment groups was observed at 12 months in the improvement by at least 1 Rutherford category of peripheral arterial disease. CONCLUSIONS: In the present study of patients with short superficial femoral artery lesions, the hypothesized absolute difference of 20% in binary restenosis at 1 year between the implantation of a single Luminexx nitinol stent and stand-alone PTA could not be demonstrated. A smaller difference requiring a larger trial might have been missed.

Predictors of death and stroke after carotid angioplasty and stenting: a subgroup analysis of the Pro-CAS data.

BACKGROUND AND PURPOSE: Little is known about the significance of patient characteristics, clinical indications, and technical details on the risk of carotid angioplasty and stenting (CAS). The purpose of this study was to test these parameters as to their predictive value for the peri-interventional risk of CAS. METHODS: Pro-CAS is a prospective, multicenter registry of CAS. Logistic regression analysis of possible predictive factors was performed on 5341 interventions that had been entered by 25 clinical centers between July 1999 and June 2005. RESULTS: The combined in-hospital mortality and stroke rate was 3.6%. The following were found to be significant predictors of peri-interventional stroke and death: center experience (< or = 50 versus 51 to 150 versus > or = 151 interventions), age, prior symptoms, primary intervention as compared with intervention for restenosis, angioplasty without stent, predilatation, and heparin dosage > 5000 IU. No statistically significant result was found for year of intervention, patient volume, gender, interval between symptoms and CAS, ocular versus neurological symptoms, side of CAS, degree of stenosis of the target lesion, presence of contralateral high-degree stenosis or occlusion, method of gaining access to the carotids, stent type, and use of a protection system. CONCLUSIONS: Our findings underline the need for dedicated training and strict credentialing rules for CAS. In addition, they might help to identify subgroups of patients at differential risk for CAS and carotid endarterectomy and yield a basis for correcting risks due to differences in case mix in reports about CAS.

Current management of renal artery stenosis.

Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary kidney, renal insufficiency (e.g. ischemic kidney disease) or pulmonary flash edema may ensue. Renal artery stenosis can be treated by revasularization, using either percutaneous angioplasty (with or without stenting) or less common open surgical procedures, both with excellent primary patency rates. However, several randomized trials of renal artery angioplasty or stenting in patients with arteriosclerotic disease have failed to demonstrate a longer-term benefit with regard to blood pressure control and renal function over medical management. It has not yet been demonstrated that renal revascularization leads to a prolongation of event-free survival. Furthermore, endovascular procedures are associated with substantial risks. If revascularization is envisaged careful patient selection, e.g. patients with refractory hypertension or progressive renal failure, is important to maximize the potential benefit.

Paclitaxel-Coated Balloon in Infrapopliteal Arteries: 12-Month Results From the BIOLUX P-II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries).

OBJECTIVES: The aim of BIOLUX P-II (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries) trial was to compare the safety and efficacy of a novel paclitaxel-coated drug-eluting balloon (DEB) versus an uncoated balloon (percutaneous transluminal angioplasty [PTA]) in de novo or native restenotic lesions of the infrapopliteal arteries in patients with claudication and critical limb ischemia. BACKGROUND: DEB have shown promising results in femoropopliteal lesions, but data for infrapopliteal lesions are scarce. METHODS: In this prospective, multicenter, randomized first-in-man study, 72 patients were randomized 1:1 to either a Passeo-18 Lux DEB (Biotronik AG, Buelach, Switzerland) (n = 36) or Passeo-18 PTA (n = 36). Follow-up assessments were scheduled at 1, 6, and 12 months, with angiographic assessment at 6 months. Adverse events were adjudicated by an independent clinical events committee, and angiographic parameters were assessed by an independent core laboratory. RESULTS: The primary safety endpoint (a composite of all-cause mortality, target extremity major amputation, target lesion thrombosis, and target vessel revascularization at 30 days) was 0% in the DEB group versus 8.3% in the PTA group (p = 0.239). The primary performance endpoint (patency loss at 6 months) was 17.1% in the DEB group versus 26.1% in the PTA group (p = 0.298), and major amputations of the target extremity occurred in 3.3% versus 5.6% of the patients at 12 months, respectively. CONCLUSIONS: The Passeo-18 Lux DEB has been proven to be safe and effective in infrapopliteal lesions with comparable outcomes to PTA.

[Renal denervation in refractory hypertension: joint statement of the German hypertension league DHL eV and the German societies of cardiology, angiology, nephrology and radiology]. / Renale Denervation bei nicht-kontrollierter arterieller Hypertonie.

Arterial hypertension is a major risk factor for cardiovascular mortality and remains insufficiently controlled in Germany. The sham controlled Symplicity HTN-3 trial did meet its primary safety endpoint but failed to meet its primary efficacy endpoint. Renal denervation can not replace established, well-proven therapies. It can only be used in selected truly resistant hypertensive patients as an additive approach and should be performed by specialized centers only. Randomized controlled trials are needed to further evaluate renal denervation.

Activation of circulating platelets in patients with peripheral arterial disease during digital subtraction angiography and percutaneous transluminal angioplasty.

Platelet activation plays a crucial role in the pathogenesis of coronary heart disease (CHD), peripheral arterial disease (PAD) and cerebral ischaemia, the three main clinical manifestations of atherosclerosis. Circulating-activated platelets are thought to trigger ischaemic complications after angiography, angioplasty and vascular surgery. We studied activation of circulating thrombocytes in patients with PAD and evaluated the influence on platelet activation of intraarterial digital subtraction angiography (DSA) and percutaneous transluminal angioplasty (PTA) in the area of the lower extremities. Our study included 16 control subjects with PAD (clinical stage IIb according to Fontaine), 25 healthy control subjects and 34 PAD patients (clinical stage IIb according to Fontaine), 14 of whom we examined during DSA, 10 during PTA and 10 which we studied during both interventions. To characterize platelet ex vivo activation, the expression of activation-dependent platelet antigens (CD62 and CD63) was measured using flow cytometry. Platelet sensitization was analysed by an additional in vitro activation. Our results show that angioplasty in peripheral vessels causes activation and presumably slight migration or a reduction in the life span of circulating thrombocytes immediately after the PTA procedure and up to 4 h afterwards. DSA was also found to be associated with platelet activation, sensitization and presumptive minor migration or shortened life span of circulating platelets. Immediately after the intervention, PTA seems to influence platelet migration or shortened lifetime of platelets to a greater extent than DSA. We postulate that this is mainly induced by dilatation. More activated and sensitized thrombocytes circulated in patients with PAD compared to healthy control subjects. This supports our assumption that preactivated platelets are particularly involved in activation, sensitization and migration processes or affected by a reduced life span.

Diagnosis of pheochromocytoma.

The purpose of this article is to give an overview on recent advances in the diagnosis, localization by imaging and treatment of pheochromocytoma. Pheochromocytoma is a mostly benign tumor (malignancy rate 10-15%) which arises from chromaffin cells with excessive catecholamine production and secretion. Most tumors are localized in the adrenals but 15-18% of the lesions are found extraadrenally (paragangliomas). Pheochromocytoma is a rare form of secondary hypertension; it can also be found as a feature of familial disease (e.g. von Hippel-Lindau disease, MEN type II) due to genetic mutations of several genes that have been identified recently. In familial pheochromocytoma molecular genetic analysis has improved the diagnostic modalities. In such patients the tumor can occur bilaterally and patients often remain normotensive until the tumor produces sufficient catecholamines to have hemodynamic effects. The extreme importance of recognizing this tumor is evident from the fact that it can be successfully removed in about 90% of the cases, whereas if unrecognized the tumor poses great risk of death or devastating complications. Diagnostic screening includes measurement of catecholamines and their metabolites (metanephrines) in plasma and/or urine. Furthermore, pharmacological testing (e.g. clonidine suppression test) may be indicated in patients with moderately elevated catecholamines or when the diagnosis is still uncertain. Several imaging techniques are applied to localize the tumor. Abdominal CT scan is still considered the "gold standard" since about 98% of the tumors lie infradiaphragmatically. Magnetic resonance imaging (MRI) and MIBG-scanning are other useful methods. Recently, positron emission tomography (PET) based techniques have also been developed. After the diagnosis is made tumor removal following pharmacological pretreatment is the decisive therapeutic measure.

Reocclusion caused by stent fracture implanted in the subclavian artery ostium: a case report.

A 47 year-old male, a woodcutter by profession, complained of severe pain in the left arm during physical stress. Eighteen months ago, a balloon-expandable stainless steel stent had been implanted in the left subclavian artery ostium. The angiography revealed a stent fracture at the origin of the left subclavian artery, this condition led to a re-obstruction of the stent. After the insertion of a self-expandable Nitinol stent, the side differences of arterial pressure and the symptoms disappeared. This is the first reported case of a stent fracture inserted at the origin of the subclavian artery without severe calcification.

MISAGO 1: first-in-man clinical trial with Misago nitinol stent.

AIMS: To evaluate a newly developed self-expanding Misago (Terumo Corp., Tokyo, Japan) nitinol stent with rapid exchange delivery catheter for the treatment of stenotic or occluded superficial femoral (SF) or popliteal arteries. METHODS AND RESULTS: MISAGO 1 clinical trial enrolled 55 patients undergoing percutaneous intervention of totally occluded or stenotic lesions in SF or popliteal arteries treated with the implantation of 81 stents in five centres across Europe. Primary endpoint was restenosis rate at six months assessed by duplex sonography. Patients (67% male) were 68+/-9 years old, 60% were smokers and 31% had diabetes. Clinical symptoms of ischaemia were present in all patients. Average lesion length was 85+/-50 mm, 64% were totally occluded and 38% classified as TASC C or D. The technical success rate was 100% while the procedural success rate was 98.2% without death, MI, stroke, or major bleeding. At six months follow-up the restenosis rate was 8.5%. One patient (1.8%) died of bronchial carcinoma and two (3.6%) underwent target vessel revascularisation. Mean ankle brachial index improved from 0.70 at baseline to 0.95 at six months while walking capacity on treadmill test improved with an average of 147 m. Rutherford index at six months demonstrated improvement of 72%, without any patients having symptom deterioration. One case of stent fracture was observed. CONCLUSIONS: The results from this first-in-man study indicate good safety and short to medium term efficacy profile of the Misago nitinol stent.

AMS INSIGHT--absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis.

Endoluminal treatment of infrapopliteal artery lesions is a matter of controversy. Bioabsorbable stents are discussed as a means to combine mechanical prevention of vessel recoil with the advantages of long-term perspectives. The possibility of not having a permanent metallic implant could permit the occurrence of positive remodeling with lumen enlargement to compensate for the development of new lesions. The present study was designed to investigate the safety of absorbable metal stents (AMSs) in the infrapopliteal arteries based on 1- and 6-month clinical follow-up and efficacy based on 6-month angiographic patency. One hundred seventeen patients with 149 lesions with chronic limb ischemia (CLI) were randomized to implantation of an AMS (60 patients, 74 lesions) or stand-alone percutaneous transluminal angioplasty (PTA; 57 patients, 75 lesions). Seven PTA-group patients "crossed over" to AMS stenting. The study population consisted of patients with symptomatic CLI (Rutherford categories 4 and 5) and de novo stenotic (>50%) or occlusive atherosclerotic disease of the infrapopliteal arteries who presented with a reference diameter of between 3.0 and 3.5 mm and a lesion length of <15 mm. The primary safety endpoint was defined as absence of major amputation and/or death within 30 days after index intervention and the primary efficacy endpoint was the 6-month angiographic patency rate as confirmed by core-lab quantitative vessel analysis. The 30-day complication rate was 5.3% (3/57) and 5.0% (3/60) in patients randomized for PTA alone and PTA followed by AMS implantation, respectively. On an intention-to-treat basis, the 6-month angiographic patency rate for lesions treated with AMS (31.8%) was significantly lower (p = 0.013) than the rate for those treated with PTA (58.0%). Although the present study indicates that the AMS technology can be safely applied, it did not demonstrate efficacy in long-term patency over standard PTA in the infrapopliteal vessels.