Venous Leak Embolization in Patients with Venogenic Erectile Dysfunction via Deep Dorsal Penile Vein Access: Safety and Early Efficacy.

PURPOSE: This all-comers registry aimed to assess safety and early efficacy of venous embolization in patients with venogenic erectile dysfunction due to venous leak in an unselected cohort. METHODS: Between October 2019 and September 2022, patients with venogenic erectile dysfunction resistant to phosphodiesterase-5-inhibitors were treated with venous embolization using ultrasound-guided anterograde access via a deep dorsal penile vein in a single center. A mix of ethiodized oil and modified cyanoacrylate-based glue n-butyl 2 cyanoacrylate (NBCA) monomer plus methacryloxy-sulpholane monomer (Glubran-2, GEM, Italy) was used as liquid embolic agent. Prior to embolization, venous leak had been verified based on penile duplex sonography and computed tomography cavernosography. Procedural success was defined as technically successful and complete target vein embolization. The primary safety outcome measure was any major adverse event 6 weeks after the procedure. The primary feasibility outcome measure was IIEF-15 (International Index of Erectile Function-15) score improvement ≥ 4 points in ≥ 50% of subjects on 6 weeks follow-up post intervention. RESULTS: Fifty consecutive patients (mean age 61.8 ± 10.0 years) with severe erectile dysfunction due to venous leak underwent venous embolization. Procedural success was achieved in 49/50 (98%) of patients with no major adverse events on follow-up. The primary feasibility outcome measure at 6 weeks was reached by 34/50 (68%) of patients. CONCLUSION: Venous leak embolization via deep dorsal penile vein access using a liquid embolic agent was safe for all and efficacious in the majority of patients with severe venogenic erectile dysfunction on 6 weeks follow-up.

Diurnal changes of lower leg volume in obese and non-obese subjects.

BACKGROUND/AIM: Obesity is a risk factor for chronic venous disease. However, the mechanisms behind this association are poorly understood. We tested the hypothesis that obese subjects have a higher diurnal leg volume increase compared with non-obese subjects. METHODS: In this prospective cohort study including obese (body mass index, BMI ≥30 kg m(-)(2)) and non-obese (BMI ≤25 kg m(-)(2)) subjects without venous insufficiency, lower leg volume was assessed by optoelectronic volumetry in the morning and in the evening. All subjects underwent duplex ultrasound and light reflection rheography (venous pump power and venous refill time, VRT) to investigate lower extremity venous function. A pedometer was carried between the morning and evening visit to assess the daily number of footsteps. A backward multivariable linear regression model was used to determine factors associated with diurnal lower leg volume increase. RESULTS: Forty-two limbs in 24 obese subjects and 29 limbs in 15 non-obese subjects were analyzed. Obese subjects had larger common femoral vein diameters (17.1±2.4 vs 15.5±2.4 mm, P<0.01) and slower peak, mean and minimal velocities (25.1±10.6 vs 44.3±14.3 cm s(-1); 6.8±2.4 vs 12.7±5.6 cm s(-1); -0.2±6.4 vs -6.3±11.9 cm s(-1); P<0.01 for all) than non-obese subjects. VRT was shorter in obese subjects (40.5±15.0 vs 51.0±12.1 s, P<0.01) and decreased significantly in the course of the day only in obese subjects (P<0.01). Obesity, male gender, CEAP (Clinical-Etiology-Anatomy-Pathophysiology) class, total time between the two visits and difference between morning and evening VRT were positively associated with higher lower leg volume increase; morning VRT and the total number of footsteps showed a negative association (P<0.04 for all). CONCLUSION: Obesity was found to be an independent predictor of higher diurnal leg volume increase. One potential mechanism is a progressive failure of venous valve function in the course of the day in obese subjects.

Standardized definitions and clinical endpoints in trials investigating endovascular repair of aortic dissections.

OBJECTIVES: Endovascular therapy is a rapidly expanding option for the treatment of patients with aortic dissection (AD) and various studies have been published. These trials, however, are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. METHODS: The DEFINE Group is a collaborative effort of an ad hoc multidisciplinary team from various specialties involved in AD therapy in Europe and the United States. DEFINE's goal was to arrive at a broad based consensus for baseline and endpoint definitions in trials for endovascular therapy of various vascular pathologies. In this project, which started in December 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. RESULTS: These efforts resulted in the present document containing proposed baseline and endpoint definitions for clinical and morphological outcomes. Although the consensus has inevitably included certain arbitrary consensus choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques. CONCLUSIONS: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in endovascular AD therapy as well as for regulatory purposes.

[Aortic aneurysms and aortic dissection: epidemiology, pathophysiology and diagnostics]. / Aortenaneurysma und -dissektion: Epidemiologie, Pathophysiologie und Diagnostik.

Aortic aneurysms and aortic dissection represent a significant health risk due to the demographic developments and current life styles. The mortality of ruptured aortic aneurysms is up to 80 % and the prevalence of aneurysms varies depending on the localization (thoracic or abdominal). Most commonly affected is the infrarenal abdominal aorta; however, there is evidence that the prevalence is diminishing but in contrast the incidence of thoracic aortic aneurysms is increasing. Aortic dissection is often fatal and is the most common acute aortic disease but the incidence is presumed to be underestimated. The pathogenesis of aortic aneurysms is manifold and is based on an interplay between degenerative, proteolytic and inflammatory processes. An aortic dissection arises from a tear in the intima which results in a separation of the aortic wall layers with infiltration of bleeding and the danger of aortic rupture. Various genetic disorders of connective tissue promote degeneration of the aortic media, most notably Marfan syndrome. Risk factors for aortic aneurysms and aortic dissection are nicotine abuse, arterial hypertension, age and male gender. Aortic aneurysms initially have an uneventful course and as a consequence are mostly discovered incidentally. The clinical course and symptoms of aortic dissection are very much dependent on the section of the aorta affected and the manifestations are manifold. Acute aortic dissection is in 80 % of cases first manifested as sudden extremely severe pain. The diagnostics and subsequent course control can be achieved by a variety of imaging procedures but the modality of choice is computed tomography.

Treatment for long-segment femoro-popliteal obstructions: initial experience with a 4-F compatible self-expanding nitinol stent and review of the literature.

AIM: The aim of this paper was to evaluate the efficacy of a novel 4-F compatible self-expanding Nitinol stent for the treatment of long femoro-popliteal obstructions. METHODS: This retrospective analysis includes patients with femoro-popliteal obstructions ≥ 120 mm in length, treated with a novel Nitinol stent (Pulsar-18) between February 2010 and December 2011. Patients were categorized as either intermittent claudication (IC) or critical limb ischemia (CLI). Primary endpoint was primary patency, secondary endpoints were target lesion revascularization (TLR). RESULTS: A total of 31 patients (IC: N=18 and CLI: N=13) were included in the present series. Mean age was 73.3 ± 10.1 years and 71% (22/31) of the patients were male. Primary intervention was performed in 77.4% (24/31) of the patients and re-do revascularization in the remaining. Mean lesion length of femoro-popliteal obstructions was 163.5 ± 32.5 mm. Technical success was obtained in all patients. Mean follow-up duration was 316 ± 198 days. Primary patency rates were 83.3% in IC and 80.0% in CLI patients at 6 months and 64.1% and 54.9% at 12 months, respectively (P=0.84). Target lesion revascularization occurred in 5.6% of IC and 20.0% of CLI patients at 6 months and in 14.1% and 36.0% at 12 months, respectively (P=0.43). CONCLUSION: Endovascular stenting of long femoro-popliteal lesions using the Pulsar-18 stent provides acceptable results with patency and restenosis rates comparable with data from literature for stenting of long femoro-popliteal obstructions.

Endovascular suitability and outcome after open surgery for ruptured abdominal aortic aneurysm.

BACKGROUND: Endovascular repair of ruptured abdominal aortic aneurysm (rAAA) has rapidly gained popularity, but superior results may be biased by patient selection. The aim was to investigate whether suitability for endovascular repair predicted survival, irrespective of technique of repair. METHODS: Two blinded investigators independently evaluated preoperative computed tomography angiograms of a consecutive cohort of patients with rAAA. Patients were categorized either 'suitable' or 'unsuitable' for endovascular repair, if assessments agreed. If assessments disagreed, they were classified 'borderline suitable'. Correlations between endovascular suitability and clinical outcome were adjusted for suspected confounding factors and tested for robustness using sensitivity analyses. RESULTS: A total of 248 patients with rAAA from January 2001 to December 2010 were included, of whom 237 (95·6 per cent) underwent open repair. Seventy patients (28·2 per cent) were classified as 'suitable' and 100 (40·3 per cent) as 'unsuitable' for endovascular repair; 63 (25·4 per cent) were considered 'borderline suitable'. Fifteen (6·0 per cent) could not be assessed and were included in the sensitivity analyses. The postoperative 30-day mortality rate was 15·3 per cent (38 deaths). Multiple logistic regression demonstrated that the odds of perioperative death increased 9·21 (95 per cent confidence interval 2·16 to 39·23) fold for 'unsuitable' rAAA (P = 0·003) and 6·80 (1·47 to 31·49) fold for 'borderline' rAAA (P = 0·014), compared with 'suitable' rAAA. This selection effect was robust across sensitivity analyses and sustained for at least 5 years of follow-up. CONCLUSION: Endovascular suitability was an independent and strongly positive predictor of survival after open repair of rAAA.

Lesion characteristics of patients with chronic critical limb ischemia that determine choice of treatment modality.

This paper will review the literature in order to define lesion characteristics that determine decision for surgical or endovascular therapy in patients with chronic critical limb ischemia (CLI). The typical pattern of disease is multilevel, infrainguinal disease. The great majority of patients with CLI can be treated by endovascular means, and the pathoanatomical pattern of disease dictates the choice of treatment modality. Long iliac artery occlusions, in particular, if associated with common femoral artery pathology and long superficial femoral artery occlusions crossing the knee joint so far remain a domain of surgery. However, there is an ongoing shift from surgery to endovascular treatment.

Chapter II: Diagnostic methods.

Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning. Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO(2)) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed.

Chapter III: Management of cardiovascular risk factors and medical therapy.

Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients. Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated. In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds. CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines. Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted. Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations.

Chapter I: Definitions, epidemiology, clinical presentation and prognosis.

The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients.

Chapter IV: Treatment of critical limb ischaemia.

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural.

Chapter V: Diabetic foot.

Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed. This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade.

Chapter VI: Follow-up after revascularisation.

Structured follow-up after revascularisation for chronic critical limb ischaemia (CLI) aims at sustained treatment success and continued best patient care. Thereby, efforts need to address three fundamental domains: (A) best medical therapy, both to protect the arterial reconstruction locally and to reduce atherosclerotic burden systemically; (B) surveillance of the arterial reconstruction; and (C) timely initiation of repeat interventions. As most CLI patients are elderly and frail, sustained resolution of CLI and preserved ambulatory capacity may decide over independent living and overall prognosis. Despite this importance, previous guidelines have largely ignored follow-up after CLI; arguably because of a striking lack of evidence and because of a widespread assumption that, in the context of CLI, efficacy of initial revascularisation will determine prognosis during the short remaining life expectancy. This chapter of the current CLI guidelines aims to challenge this disposition and to recommend evidentially best clinical practice by critically appraising available evidence in all of the above domains, including antiplatelet and antithrombotic therapy, clinical surveillance, use of duplex ultrasound, and indications for and preferred type of repeat interventions for failing and failed reconstructions. However, as corresponding studies are rarely performed among CLI patients specifically, evidence has to be consulted that derives from expanded patient populations. Therefore, most recommendations are based on extrapolations or subgroup analyses, which leads to an almost systematic degradation of their strength. Endovascular reconstruction and surgical bypass are considered separately, as are specific contexts such as diabetes or renal failure; and critical issues are highlighted throughout to inform future studies.

Repair of ruptured abdominal aortic aneurysm in octogenarians.

OBJECTIVE: To determine whether advanced age was independently associated with prohibitive surgical risks or impaired long-term prognosis after ruptured aortic aneurysm repair. DESIGN: Post-hoc analysis of prospective cohort. MATERIALS: Consecutive patients undergoing ruptured aneurysm repair between January 2001 and December 2010 at a tertiary referral centre. METHODS: Surgical mortality (i.e., <30 days) was compared between octogenarians and younger patients using logistic regression modelling to adjust for suspected confounders and to identify prognostic factors. Long-term survival was compared with matched national populations. RESULTS: Sixty of 248 involved patients were octogenarians (24%) and almost all were offered open repair (n = 237). Surgical mortality of octogenarians was 26.7% (adjusted odds ratio (OR) 2.1; 95% confidence interval (CI), 0.9-5.2) and confounded by cardiac disease. Hypovolaemic shock predicted perioperative death of octogenarians best (OR 5.1; 95%CI, 1.1-23.4; P = 0.037). After successful repair, annual mortality of octogenarians averaged 13.7% vs. 5.2% for younger patients. At 2 years, octogenarian survival was at 94% of the expected 'normal' survival in the general population (vs. 96% for younger patients). CONCLUSIONS: Surgical mortality of ruptured aneurysm repair was not independently related to advanced age but mainly driven by cardiac disease and manifest hypovolaemic shock. An almost normal long-term prognosis of aged patients after successful repair justifies even attempts of open repair, particularly in carefully selected patients.