Preprocedural imaging modalities in patients undergoing iliocaval venous recanalization and stent placement.

PURPOSE: To determine the diagnostic accuracy of preinterventional imaging modalities in patients being evaluated for iliocaval venous recanalization and stent placement. METHODS: Consecutive patients with iliocaval postthrombotic obstructions or nonthrombotic iliac vein lesions (NIVL), who were scheduled for recanalization, underwent duplex ultrasound (DUS), magnetic resonance venography (MRV), multiplanar venography (MPV), and intravascular ultrasound (IVUS). The diagnostic accuracies of DUS, MRV, and MPV were analyzed using IVUS as reference. RESULTS: A total of 216 limbs in 108 patients (80 patients with postthrombotic obstructions, 28 patients with NIVL) were examined. In patients with postthrombotic obstructions, the diagnostic sensitivities for the detection of lesions of the common femoral vein were 81% (95% CI 71-89%) for DUS, 76% (95% CI 65-85%) for MRV, and 86% (95% CI 76-93%) for MPV. The sensitivities for detecting lesions of the iliac veins were 96% (95% CI 89-99%) for DUS, 99% (95% CI 92-100%) for MRV, and 100% (95% CI 94-100%) for MPV. Regarding the inferior vena cava, the sensitivities were 44% (95% CI 24-65%) for DUS, 52% (95% CI 31-73%) for MRV, and 70% (95% CI 47-86%) for MPV. The sensitivities for detecting NIVL were 58% (95% CI 34-79%) for DUS, 90% (95% CI 68-97%) for MRV, and 95% (95% CI 73-99%) for MPV. CONCLUSION: In patients scheduled for recanalization of iliocaval postthrombotic obstructions, the sensitivities of DUS, MRV, and MPV were similar. In patients with suspected inferior vena cava involvement and in patients with NIVL, additional imaging with MR or conventional venography is required.

Development of a localization-based algorithm for the prediction of leg ulcer etiology.

BACKGROUND: Diagnostic work-up of leg ulcers is time- and cost-intensive. This study aimed at evaluating ulcer location as a diagnostic criterium and providing a diagnostic algorithm to facilitate differential diagnosis. PATIENTS AND METHODS: The study consisted of 277 patients with lower leg ulcers. The following five groups were defined: Venous leg ulcer, arterial ulcers, mixed ulcer, arteriolosclerosis, and vasculitis. Using computational surface rendering, predilection sites of different ulcer types were evaluated. The results were integrated in a multinomial logistic regression model to calculate the likelihood of a specific diagnosis depending on location, age, bilateral involvement, and ulcer count. Additionally, neural network image analysis was performed. RESULTS: The majority of venous ulcers extended to the medial malleolar region. Arterial ulcers were most frequently located on the dorsal aspect of the forefoot. Arteriolosclerotic ulcers were distinctly localized at the middle third of the lower leg. Vasculitic ulcers appeared to be randomly distributed and were markedly smaller, multilocular and bilateral. The multinomial logistic regression model showed an overall satisfactory performance with an estimated accuracy of 0.68 on unseen data. CONCLUSIONS: The presented algorithm based on ulcer location may serve as a basic tool to narrow down potential diagnoses and guide further diagnostic work-up.

Closure of Post-thrombotic Iliac Arteriovenous Fistulas by Iliac Vein Recanalization.

PURPOSE: The purpose of this study was to report the closure of iliac arteriovenous fistulas associated with a post-thrombotic iliac vein occlusion by iliac venous stent recanalization. CASE REPORT: An 80-year-old woman presented with a worsening painful swelling of her left leg after an iliofemoral deep vein thrombosis 6 months ago. Duplex ultrasound and magnetic resonance venography revealed a post-thrombotic obstruction of her iliac veins as well as several arteriovenous fistulas between branches of her left external and internal iliac arteries and adjacent diseased venous segments. In a first attempt, coil embolization did not sustainably close these iliac arteriovenous fistulas. Direct stent recanalization of the chronically diseased iliofemoral venous segment, however, resulted in an immediate closure of arteriovenous shunt flow and subsequent improvement of clinical symptoms. Six months after iliac vein stent recanalization, still no fistulas could be detected any more, venous stents were fully patent, and the patient was free of symptoms. CONCLUSION: Post-thrombotic iliofemoral obstructions might be associated with the development of arteriovenous fistulas. Direct stent recanalization of the chronically occluded veins results in closure of related arteriovenous fistulas. CLINICAL IMPACT: This case suggests that the combined occurrence of post-thrombotic venous obstructions with arteriovenous fistulas, which are related to aforementioned venous lesions, should be evaluated for primary venous stent recanalization rather than fistula embolization.

Microcirculatory assessment of vascular diseases.

The term "microcirculation" refers to the terminal vascular network of the body, which includes arterioles, capillaries, venules as well as initial lymphatic vessels. Additionally, it insinuates to their unique function in thermoregulation, fluid balance, maintenance of cellular exchange, and metabolism. Disturbances of microvascular function were identified to precede macrovascular involvement in the presence of cardiovascular risk factors and is the hallmark of terminal disease stages like critical limb or acral ischemia. Nevertheless, despite its obvious significance in vascular medicine assessment of microvascular function became increasingly neglected in the clinical institutions during the last decades and seems to play a subordinary role in medical education. We therefore provide an overview over relevant and clinically practicable methods to assess microcirculation in vascular medicine with critical estimations of their pros and cons and their perspectives in the future.

Relation of Nailfold Capillaries and Autoantibodies to Mortality in Patients With Raynaud Phenomenon.

BACKGROUND: In incipient Raynaud phenomenon, nailfold capillaroscopy and autoantibody tests are obtained to screen for an emerging connective tissue disease. Whether the presence of abnormal nailfold capillaries and autoantibodies are related to mortality in patients with incipient Raynaud phenomenon is not known. METHODS AND RESULTS: In 2958 consecutive patients (78% women, median age 45 years) with incipient Raynaud phenomenon without previously known connective tissue disease, nailfold capillaroscopy and laboratory tests for antinuclear antibodies (ANA) and ANA subsets were obtained at initial presentation. During a median follow-up period of 9.3 years, 227 women (9.9% of female patients) and 129 men (20% of male patients) with Raynaud phenomenon died. In comparison with a demographically matched standard population, survival was poorer in patients with Raynaud phenomenon (log-rank test P<0.0001). In patients with Raynaud phenomenon, mortality was higher in men than in women (P<0.0001, Cox proportional hazards model). In women, the presence of abnormal nailfold capillaries, ANA, and anti-Scl-70 antibodies were related to an increase in all-cause mortality. The conjoint presence of abnormal nailfold capillaries and autoantibodies was associated with the highest mortality rates. In men, abnormal nailfold capillaries, and ANA and ANA subsets, as well, were not related to survival. In both sexes, patients' age and serum creatinine were associated with mortality. CONCLUSIONS: In Raynaud phenomenon, male sex, age, and serum creatinine are related to mortality. Abnormal nailfold capillaries and autoantibodies are associated with an increase in all-cause mortality in female patients, but not in male patients with Raynaud phenomenon.

Impact of age and gender on microvascular function.

BACKGROUND: Microcirculatory function can be assessed by postocclusive reactive hyperaemia (PORH) using laser Doppler fluxmetry. Previous studies have shown that PORH reveals microvascular damage at an early stage. In particular, at younger ages, PORH might depend on age and gender. To implement PORH into a larger scale of clinical studies, one has to be aware of the influence of age and gender on microcirculation. The aim of this study was to assess the impact of age and gender on microcirculatory function during adolescence. MATERIALS AND METHODS: Within the scope of an epidemiological project, 896 children and adolescents underwent assessment of PORH by laser Doppler fluxmetry. Microcirculatory parameters during PORH (baseline perfusion, biological zero, peak perfusion, time to peak perfusion and recovery time) were analysed in relation to age (by tertiles) and gender. RESULTS: Baseline perfusion, biological zero and peak perfusion were lower in children/adolescents in the upper age tertile (12·3-18·1 years) than in the middle (9·8-12·2 years) and lower (4·3-9·7 years) age tertiles (P < 0·0001). In the total of participants, baseline perfusion, biological zero and peak perfusion were higher in males than in females (P < 0·0001). Analysing microcirculatory parameters as a function of age and gender, the sex differences were only apparent in the upper and the middle age tertiles, but not in the lower. CONCLUSIONS: During adolescence, PORH is a function of age. At higher age, microvascular reactivity considerably depends on gender, whereas no sex differences are present at younger ages.

A RAND/UCLA-Modified VAS Study on Telemedicine, Telehealth, and Virtual Care in Daily Clinical Practice of Vascular Medicine.

Background: Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. Methods: A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion. The Telemedicine Vascular Medicine Working Group included 32 experts from Europe evaluating the appropriateness of each clinical practice recommendation based on published RAND/UCLA methodology in two rounds. Results: In the first round, 60.9% of clinical practice recommendations were rated as appropriate, 35.9% as uncertain, and 3.1% as inappropriate. The strongest agreement (a median value of 10) was reached on statements regarding the usefulness of telemedicine during the 2019 coronavirus disease (COVID-19) pandemic, its usefulness for geographical areas that are difficult to access, and the superiority of video calls compared to phone calls only. The lowest degree of agreement (a median value of 2) was reported on statements regarding the utility of telemedicine being limited to the COVID-19 pandemic and regarding the applicability of teleconsultation in the diagnosis and management of abdominal aortic aneurysm. In the second round, 11 statements were re-evaluated to reduce variability. Conclusions: This study highlights the levels of agreement and the points that raise concern on the use of telemedicine in vascular medicine. It emphasizes the need for further clarification on various issues, including infrastructure, logistics, and legislation.

Healing process of venous ulcers: the role of microcirculation.

In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well-defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1·35; lower-upper quartiles 0·71-1·83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2·22; 1·12-2·33; P = 0·0024) when compared with NGTA, in combination with a significant increase in CD (1·75; 0-3; P = 0·0054). In scar, the LDP was similar to that in the NGTA (1·03; 0·77-1·83; P = 0·278), combined with the highest CD (5·75; 4·5-8) in comparison with the previous stages of the area (for both pairs, P < 0·0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low.

Micro- and Macrovascular Effects of Inflammation in Peripheral Artery Disease-Pathophysiology and Translational Therapeutic Approaches.

Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus, tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote pro-inflammatory pathways also contributing to pro-coagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing the molecular and clinical effects of inflammatory processes on the micro- and macrovasculature with a focus on peripheral artery disease.

Associations between nailfold capillary aberrations and autoantibodies in children and adults with Raynaud's phenomenon.

OBJECTIVE: To characterise associations between individual nailfold capillary aberrations with autoantibodies in a cross-sectional study on children and adults with Raynaud's phenomenon (RP). METHODS: Consecutive children and adults with RP and without previously known connective tissue disease (CTD) systemically underwent nailfold capillaroscopy and laboratory tests for the presence of antinuclear antibodies (ANA). The prevalence of individual nailfold capillary aberrations and ANA was assessed, and the associations between individual nailfold capillary aberrations and ANA were analysed separately in children and adolescents. RESULTS: In total, 113 children (median age 15 years) and 2858 adults (median age 48 years) with RP and without previously known CTD were assessed. At least one nailfold capillary aberration was detected in 72 (64%) of included children and in 2154 (75%) of included adults with RP (children vs adults p<0.05). An ANA titre ≥1:80, ≥1:160 or≥1:320 was observed in 29%, 21% or 16% of included children, and in 37%, 27% or 24% of screened adults, respectively. While the occurrence of individual nailfold capillary aberrations was related to the presence of an ANA titre of ≥1:80 in adults (reduced capillary density, avascular fields, haemorrhages, oedema, ramifications, dilations and giant capillaries: each p<0.001), no comparable association between nailfold capillary aberrations and ANA was observed in children with RP without previously known CTD. CONCLUSION: In contrast to adults, the association between nailfold capillary aberrations and ANA might be less pronounced in children. Further studies are warranted to validate these observations in children with RP.

Microvascular function is impaired in children with morbid obesity.

Children's obesity is a growing problem in Western societies. We hypothesized that morbid obesity (body mass index [BMI] > 99.5th percentile) might affect microvascular function at an early stage. Therefore, we assessed the microvascular function of 41 obese children (13.2 ± 2.8 years, BMI 32.9 ± 6.6) in comparison to 91 healthy controls (12.7 ± 2.1 years, BMI 18.2 ± 2.5) by post-occlusive reactive hyperemia measured by a laser Doppler: baseline perfusion, biological zero (defined as 'no-flow' laser Doppler signal during supracystolic occlusion), peak perfusion (following occlusion), time to peak perfusion and recovery time (time until resuming baseline perfusion) were recorded and compared between both groups. Peak perfusion was higher in children with morbid obesity than in controls (1.67 ± 0.76 AU [arbitrary units] vs 1.26 ± 0.5 AU, p < 0.001). Consecutively, recovery time was longer in children with morbid obesity (118.21 ± 34.64 seconds) than in healthy children (83.18 ± 35.08 seconds, p < 0.001). In conclusion, higher peak perfusion and prolonged recovery time in children with morbid obesity seem to reflect microvascular dysfunction due to an impaired vasoconstrictive ability of precapillary sphincters.

Correlation of infrared thermography and skin perfusion in Raynaud patients and in healthy controls.

BACKGROUND: We aimed to investigate the correlation of infrared thermography (IT) with laser Doppler perfusion imager (LDPI) among patients with primary Raynaud's phenomenon and healthy controls. METHODS: Forty-seven individuals were included: we examined 25 patients with primary Raynaud's phenomenon and 22 age and gender matched healthy controls. IT of the volar surface of the subjects' left hands was performed to record skin temperature while skin perfusion of the same area was determined using LDPI. All measurements were obtained at room temperature (baseline measurements) and following standardized cold provocation. RESULTS: Good correlation of baseline measurements was found between IT and LDPI in primary Raynaud patients and healthy controls (r=0.868, p<0.0001 vs. r=0.790, p<0.0001). Following cold challenge, correlation was weaker in both groups (r=0.742 vs. r=0.766, p<0.0001). Correlation after cold provocation was statistically significant among patients with primary Raynaud's phenomenon in contrast to controls (Chi Quadrat, p=0.023 vs. p=0.306). CONCLUSION: A significant correlation was found between IT and LDPI in primary Raynaud patients and in healthy controls (r=0.868 and r=0.742, both p<0.0001). Following cold provocation, correlation decreases in both groups. Thus, at room temperature IT might substitute for skin perfusion measured by LDPI.

Microcirculation in mixed arterial/venous ulcers and the surrounding skin: clinical study using a laser Doppler perfusion imager and capillary microscopy.

To treat mixed skin ulcers effectively, it is important to investigate skin microcirculation in greater detail. Therefore, we used laser Doppler perfusion imaging and capillary microscopy for assessing both subpapillary and nutritive microcirculation in four defined regions of the skin in 17 patients with mixed ulcers caused by a combination of peripheral arterial occlusive disease and chronic venous insufficiency. Laser Doppler area flux was significantly higher in the ulcer areas than in the areas without granulation tissue and those in intact skin. The flux in the scars was higher than that in the intact skin or in the ulcer areas without granulation tissue. Capillary density in the intact skin was higher than the densities in nongranulation tissue areas, granulation areas, and scar areas (p<0.001 for all comparisons). To conclude, the ulcer areas without granulation tissue did not show a healing tendency due to poor subpapillary and nutritive perfusion; the granulation tissue exhibited high subpapillary perfusion as a sign of healing. In the scars, sufficient blood supply could be detected in both layers as a sign of an almost complete healing process. Blood supply in the intact skin is, however, already affected by distorted microcirculation in the ulcers.

Drug coated balloons in the superficial femoral artery.

Despite the progress in endovascular treatment of patients with peripheral arterial disease, restenosis remains the major drawback, especially in patients with femoropopliteal lesions. To reduce neointimal proliferation and subsequent restenosis the use of antiproliferative drug eluting devices was implemented in the endovascular treatment of femoropopliteal disease. Aiming to use the favorable effects of these antiproliferative agents and to reduce foreign body exposure in affected arteries, drug coated balloons (DCB) have been developed. Up to now, several randomized controlled trials have consistently demonstrated the superiority of DCB over uncoated balloon angioplasty in the treatment of femoropopliteal lesions. Similarly, DCB appear to have favorable effects on vessel patency in the treatment of femoropopliteal in-stent restenosis. However, there still is a need for further studies, especially addressing different lesion characteristics as well as the combinations of particular treatment modalities.

Microvascular function in women with former gestational diabetes: A cohort study.

OBJECTIVE: In the long term, diabetes mellitus is potentially associated with the occurrence of microvascular damage. This study sought to assess whether a history of prior gestational diabetes mellitus is associated with long-term effects on the women's microcirculation. METHODS: Within the scope of a long-term follow-up of the 'Viennese Post-Gestational Diabetes Project', women with prior gestational diabetes mellitus as well as women with previous pregnancy but with no history of gestational diabetes mellitus (controls) were enrolled in this cross-sectional study. Microvascular function was assessed by post-occlusive reactive hyperaemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded and compared between both groups. RESULTS: Microvascular function was assessed in 55 women with prior gestational diabetes mellitus (46.1 ± 4.6 years) and 32 women with previous pregnancy but without prior gestational diabetes mellitus (42.9 ± 5.3 years). The mean period of time between delivery and the assessment of microvascular function was 16.2 ± 5.2 years in women with prior gestational diabetes mellitus group and 14.2 ± 4.8 years in controls. Regarding microvascular function, baseline perfusion, biological zero, peak perfusion, time to peak and recovery time did not differ between women with prior gestational diabetes mellitus and controls (all p > 0.05). CONCLUSION: In the long term, microvascular function appears not to be impaired in women with prior gestational diabetes mellitus.

Can we clinically recognize a vascular depression? The role of personality in an expanded threshold model.

The vascular depression (VD) hypothesis postulates that cerebrovascular disease may "predispose, precipitate, or perpetuate" a depressive syndrome in elderly patients. Clinical presentation of VD has been shown to differ to major depression in quantitative disability; however, as little research has been made toward qualitative phenomenological differences in the personality aspects of the symptom profile, clinical diagnosis remains a challenge.We attempted to identify differences in clinical presentation between depression patients (n = 50) with (n = 25) and without (n = 25) vascular disease using questionnaires to assess depression, affect regulation, object relations, aggressiveness, alexithymia, personality functioning, personality traits, and counter transference.We were able to show that patients with vascular dysfunction and depression exhibit significantly higher aggressive and auto-aggressive tendencies due to a lower tolerance threshold. These data indicate that VD is a separate clinical entity and secondly that the role of personality itself may be a component of the disease process. We propose an expanded threshold disease model incorporating personality functioning and mood changes. Such findings might also aid the development of a screening program, by serving as differential criteria, ameliorating the diagnostic procedure.

Relationship of age and body mass index to skin temperature and skin perfusion in primary Raynaud's phenomenon.

OBJECTIVE: To assess the relationship of age and body mass index (BMI) to skin temperature and perfusion in patients with primary Raynaud's phenomenon (RP) compared with controls. METHODS: Patients with RP as well as age- and sex-matched controls underwent external cold provocation by exposure to 20 °C water for 1 minute. Before and after cold provocation, skin temperature and skin perfusion were measured. RESULTS: Twenty-six patients with RP (20 women and 6 men; median age 41.9 years) and 22 controls (17 women and 5 men; median age 42.9 years) were studied. In RP patients, cold exposure led to a median change in skin temperature of -7% (interquartile range [IQR] -13.1, -4.1) and to a median change in skin perfusion of -26.4% (IQR -36.2, 2.9). In controls, skin temperature changed by -15.7% (IQR -18.3, -11.6) and skin perfusion by -33% (IQR -53.3, -1.1) upon cold exposure. In patients with RP, age and BMI were related to skin temperature (for age, r = 0.683, P < 0.0001; for BMI r = 0.657, P < 0.0001) and skin perfusion (for age, r = 0.595, P = 0.002; for BMI, r = 0.653, P < 0.0001), while no association was found in controls. The cold-induced decrease in skin temperature was inversely related to age (r = -0.518, P = 0.003) and BMI (r = -0.662, P < 0.0001) in patients with RP; correlations were not observed in controls. The cold-induced change in skin perfusion was not related to age or BMI in either group. CONCLUSION: The cold-induced decrease in skin temperature is related to age and BMI in patients with RP but not in controls. Further studies are needed to clarify the pathophysiology of digital ischemia in primary RP.

Outcome of conservative medical treatment of patients with infrarenal abdominal aortic aneurysms.

OBJECTIVE: Since non-invasive diagnostic methods have become available and screening programs have become popular, abdominal aortic aneurysms are more frequently being detected at an early stage of the disease. We analyzed the course of conservatively treated patients with infrarenal abdominal aortic aneurysms (AAA), and determined independent risk factors for aneurysm expansion. METHODS: The study was designed as a retrospective-cohort study including 110 consecutive patients with AAA. Cardiovascular risk factors, comorbidities, current medication, and the findings of color coded duplex sonography and computed tomography were recorded. Ninety-two conservatively treated patients were re-investigated every 6 or 12 months (depending on an initial aneurysm size of > 45 mm or < 45 mm respectively) after initial detection by color coded duplex sonography. We performed a multivariate Cox regression analysis to determine independent predictors of diameter progression (diameter increase > or = 5 mm). RESULTS: We found AAA expansion in 46 conservatively treated patients (50%) during the median follow up period of 23 months (IQR 13 to 33), but no rupture occurred. Baseline diameter > 45 mm (HR 2.3, 95% CI 1.0 to 5.3, P = .04) and signs of aortic dissection in duplex ultrasound (HR 2.2, 1.0 to 4.6, P = .04) were independently associated with aneurysm expansion. The presence of an intraluminal thrombus showed a trend towards higher rates of disease progression (HR 2.6, 95% CI 0.9 to 7.6, P = .08). CONCLUSION: Patients with an aneurysm diameter > 45 mm or ultrasound signs of aortic dissection have an increased risk for AAA progression and need careful evaluation, optimization of risk factors and close (six-month) follow-up intervals. For patients with an aneurysm diameter below 45 mm and without additional risk factors, follow-up intervals of 12 months seem to be safe.