Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease.

BACKGROUND: Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population. METHODS: In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation. RESULTS: Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan-Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates. CONCLUSION: Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.

Cardiac biomarkers but not measures of vascular atherosclerosis predict mortality in patients with peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) becomes more prevalent with advancing age and is associated with elevated risk of cardiovascular events and shortened life expectancy. We investigated the prognostic performance of cardiac and vascular biomarkers in a cohort of PAD patients. METHODS: A total of 95 PAD patients were enrolled (mean age 68 years, range 47 to 86 years, 73 males). Carotid intima-media thickness (cIMT), ankle brachial index (ABI), high sensitive cardiac troponin T, and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) were measured. RESULTS: During a median follow-up time of 9.5 years, 44 patients died and 51 patients survived. Upon Kaplan-Meier survival analysis hs-TnT (P < .001) or NT-proBNP levels (P < .001) above the median but not cIMT above the median (P = .488) or ABI below the median (P < .436)were associated with reduced survival rate. Upon univariate cox regression and after adjustment for age, gender, prior cerebral artery disease, and diabetes mellitus only the association between hs-cTnT and mortality remained significant (HR 1.93, 95% CI 1.33-2.79, P < .001). In receiver operating curve analysis hs-cTnT (area under the curve [AUC]: 0.77, 95% CI: 0.67-0.87, P < .001) NT-proBNP (AUC: 0.74, 95% CI: 0.64-0.84, P < .001) as well as hs-cTnT, and NT-proBNP combined (AUC: 0.79, 95% CI: 0.69-0.88, P < .001) were superior to cIMT (AUC: 0.64, 95%, CI: 0.53-0.76, P = .022) and ABI (AUC: 0.57, 95% CI: 0.44-0.68, P = .313) in discriminating risk for mortality. CONCLUSION: hs-cTnT and NT-proBNP should be taken into account for prognosis of patients with PAD.

Correction to: Design and rationale of the non-interventional, edoxaban treatment in routiNe clinical prActice in patients with venous ThromboEmbolism in Europe (ETNA-VTE-Europe) study.

[This corrects the article DOI: 10.1186/s12959-018-0163-7.].

Design and rationale of the non-interventional, edoxaban treatment in routiNe clinical prActice in patients with venous ThromboEmbolism in Europe (ETNA-VTE-Europe) study.

BACKGROUND: Venous thromboembolism (VTE, including deep vein thrombosis [DVT] and pulmonary embolism [PE]) has an annual incidence rate of 104-183 per 100,000 person-years. After a VTE episode, the two-year recurrence rate is about 17%. Consequently, effective and safe anticoagulation is paramount. Edoxaban is a direct oral anticoagulant (DOAC) approved VTE treatment. Current safety and efficacy data are derived from clinical trials, and information about treatment durations beyond 12 months are not available. METHODS: ETNA-VTE-Europe is an 18-month prospective, single-arm, non-interventional, multinational post-authorisation safety study. Approximately 310 sites across eight European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Switzerland and the United Kingdom) will participate in the study, with the intention to represent the regional distributions of centres, healthcare settings and specialties. An estimated cohort of 2700 patients will be recruited, the only enrolment criteria being acute symptomatic VTE, no participation in an interventional study, and treating physician decision to prescribe edoxaban independently from the registry. Data from patient medical records and/or telephone interviews will be collected at baseline, 1, 3, 6, 12 and 18 months. The primary objective is to evaluate the 18-month rate of symptomatic VTE recurrence in patients with VTE treated with edoxaban outside a clinical trial. The co-primary objective is to evaluate the real-world rates of bleeding and adverse drug reactions. Secondary outcomes include rates of other patient-relevant safety events, adherence to and discontinuation of edoxaban. Furthermore, 12-month ETNA-VTE-Europe data will be considered in the context of those for patients receiving different anticoagulants in the PREFER in VTE registry and Hokusai-VTE clinical trial. CONCLUSIONS: ETNA-VTE-Europe will allow the safety and effectiveness of edoxaban to be evaluated over an extended period in acute symptomatic VTE patients encountered in routine clinical practice. Findings will be informative for European practitioners prescribing edoxaban as part of real-world VTE treatment/prevention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02943993.

Sensitivities of in vivo markers of arterial organ damage in patients with peripheral atherosclerosis.

BACKGROUND: Biomarkers of vascular diseases such as ankle-brachial index (ABI), peripheral pulse pressure (pPP), central pulse pressure (cPP), and pulse wave velocity (PWV) allow assessment of arterial organ damage (AOD). However, the utility of markers other than ABI in patients with peripheral arterial disease (PAD), which are also associated with a significant increase of cardiovascular events, remains unclear. PATIENTS AND METHODS: Asymptomatic (n = 21) and symptomatic patients (n = 46) with a positive sonography for PAD or history of lower limb revascularization were included. ABI, pPP, cPP, and PWV were assessed. PWV were performed using a brachial cuff-based method (aortic PWV (aPWV)) and oscillography (carotid-femoral pulse wave velocity (cfPWV)), respectively. The two methods for PWV were compared using Bland Altman analysis. Sensitivities of ABI, pPP, cPP, cfPWV, and aPWV for AOD were calculated. RESULTS: Sixty-seven patients (35.8 % female, mean age 69, range 39-91 years) had a significantly higher aPWV than cfPWV (median 10.5 m/s (IQR: 8.8-12.65 m/s) vs. median 9.0 m/s (IQR: 7.57-10.55 m/s), p = 0.0013). There was no correlation between cfPWV and age (r = 0.311, p = 0.116). Bland Altman analysis revealed a mean difference of -1.04 (-2SD; -6.38 to + 2SD; 4.31). The sensitivities for AOD were 68.7 % for ABI, 61.2 % for aPWV, 40.3 % for cfPWV, 31.3 % for peripheral PP, and 10.4 % for central aortic PP (p < 0.001). CONCLUSIONS: Brachial-derived aPWV differs from the gold standard assessment (cfPWV), which may be underestimated in PAD due to atherosclerotic obstructions along the aorto-iliac segment. The sensitivities of noninvasive in vivo markers of AOD vary widely and tend to underestimate the actual presence of AOD.

ESVM guidelines - the diagnosis and management of Raynaud's phenomenon.

Regarding the clinical diagnosis of Raynaud's phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud's phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud's phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment.

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: Twelve-Month Results of the DEFINITIVE AR Study.

BACKGROUND: Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. METHODS AND RESULTS: DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency-A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB (P=0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P=0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB (P=0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB (P=0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB (P=0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB (P=0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB (P=0.86). CONCLUSIONS: DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique Identifier: NCT01366482.

Percutaneous sclerotherapy for spongiform venous malformations - analysis of patient-evaluated outcome and satisfaction.

BACKGROUND: Congenital venous malformations are frequently treated with sclerotherapy. Primary treatment goal is to control the often size-related symptoms. Functional impairment and aesthetical aspects as well as satisfaction have rarely been evaluated. PATIENTS AND METHODS: Medical records of patients who underwent sclerotherapy of spongiform venous malformations were reviewed and included in this retrospective study. The outcome of sclerotherapy as self-reported by patients was assessed in a 21 item questionnaire. RESULTS: Questionnaires were sent to 166 patients with a total of 327 procedures. Seventy-seven patients (48 %) with a total of 159 procedures (50 %) responded to the survey. Fifty-seven percent of patients were male. The age ranged from 1 to 38.1 years with a median age of 16.4 years. The lower extremities were the most common treated area. Limitations caused by the venous malformation improved in the majority of patients (e.g. pain improvement 87 %, improvement of swelling 83 %) but also worsening of symptoms occurred in a minority of cases. Seventy-seven per cent would undergo sclerotherapy again. CONCLUSIONS: Sclerotherapy for treatment of venous malformations results in significant reduction of symptoms. Multiple treatments are often needed, but patients are willing to undergo them.

Assessment of PTEN-associated vascular malformations in a patient with Bannayan-Riley-Ruvalcaba syndrome.

Misdiagnosis of phosphatase and tensin homologue hamartoma syndromes is common. Correct diagnosis has a relevant impact on patients, as the risk of malignancies is high and treatment options are limited. We report the case of a 24-year-old man who presented with symptomatic vascular intramuscular lesions of the left forearm and right calf, macrocephaly, post Hashimoto thyroiditis, a multicystic intracranial paratrigonal lesion, lentiginous hyperpigmented maculae on the foreskin and multiple skin lesions. MRI showed extended fibrofatty changes and malformed vessels in the forearm and calf lesions, also, arteriovenous shunting was present in these lesions. The patient had been treated by embolisation and surgically in the past, with limited results. A multidisciplinary assessment and genetic counselling were undertaken and a surveillance programme was initiated. Treatment options of the symptomatic vascular lesions include excision or possibly cryoablation. Physiotherapy to prevent progression of the contractures should be initiated meanwhile.

ß-Blockers and Vascular Hemodynamics in Patients With Peripheral Arterial Disease.

Aortic augmentation index (AIx) is a marker of central aortic pressure burden and is modulated by antihypertensive drugs. In patients with peripheral arterial disease (PAD) undergoing antihypertensive treatment, aortic pressures parameters, heart rate-adjusted augmentation index (AIx75), and unadjusted AIx were determined. The (aortic) systolic and diastolic blood pressure did not differ between PAD patients who were taking ß-blockers (n=61) and those who were not taking ß-blockers (n=80). In patients taking ß-blockers, augmentation pressure and pulse pressure were higher than in patients who did not take ß-blockers (augmentation pressure, P=.02; pulse pressure, P=.005). AIx75 was lower in PAD patients taking ß-blockers than in patients not taking ß-blockers (P=.04), while the AIx did not differ between PAD patients taking and not taking ß-blockers. The present study demonstrates that ß-blockers potentially affect markers of vascular hemodynamics in patients with PAD. Because these markers are surrogates of cardiovascular risk, further studies are warranted to clarify the impact of selective ß-blocker treatment on clinical outcome in patients with PAD.

Efficacy of compression stockings in preventing post-thrombotic syndrome in patients with deep venous thrombosis: a systematic review and metaanalysis.

BACKGROUND: Here, we update an earlier systematic review on the preventive efficacy of active compression stockings in patients with diagnosed proximal deep venous thrombosis (DVT) by including the results of recently published trials. The aims are to synthesize the results of the original studies, and to identify details to explain heterogeneous results. METHODS: We searched the Cochrane Library, PubMed, Scopus, and Medline for original studies that compared the preventive efficacy of active compression stockings with placebo or no compression stockings in patients with diagnosed proximal DVT. Only randomized controlled trials (RCTs) were included. RESULTS: Five eligible RCTs with a total of 1393 patients (sample sizes ranged from 47 to 803 patients) were included. In three RCTs, patients started to wear compression stockings, placebo stockings or no stockings within the first three weeks after the diagnosis of DVT. The results of two RCTs indicate a statistically significant reduction in post-thrombotic syndrome (PTS) of 50% or more after two or more years. The result of one RCT shows no preventive effect of compression stockings at all. Due to the heterogeneity of the study results, we refrained from pooling the results of the RCTs. In a further RCT, randomization to groups with and without compression stockings took place six months after the diagnosis of DVT, and in another RCT, only patients with the absence of PTS one year after the diagnosis of DVT were analyzed. One RCT revealed a significant reduction in symptoms, whereas another RCT failed to show any benefit of using compression stockings. CONCLUSIONS: At this time, it does not seem to be justifiable to entirely abandon the recommendations regarding compression stockings to prevent PTS in patients with DVT. There is evidence favoring compression stockings, but there is also evidence showing no benefit of compression stockings.

Vertebral and internal mammary artery steal syndrome in patients with hemodialysis access.

BACKGROUND: Increased flow in the subclavian artery feeding a vascular access for hemodialysis can induce steal phenomena in the vertebral (VA) and internal mammary artery (IMA). The aim of this study was to describe the hemodynamic effects of access flow on the VA and IMA in patients with native fistulas and grafts. PATIENTS AND METHODS: Peak systolic (PSV) and end diastolic (EDV) velocity measurements of the VA, IMA and carotid arteries, as well as flow volume measurements of the subclavian artery, were performed. Flow measurements at the side of the vascular access were compared with the contralateral side. Fifty-five patients were consecutively included, most with a radio-cephalic fistula on the left arm with a mean shunt volume of 1156 ml/min. RESULTS: Pathologic flow patterns were observed in the ipsilateral VA in four patients (7.3 %); contralateral VA flow was normal in all patients. Peak systolic velocity of the VA was significantly decreased at the side of the shunt arm with a PSV of 42.6 ± 11.8 cm/s compared to 48.4 ± 15.6 cm/s contralateral (p < 0.05). The IMA flow pattern were normal in all patients. The PSV of the IMA was significantly decreased (p < 0.01) at the side of the shunt arm (87.5 ± 29.1 cm/s) compared to the non-shunt arm (95.9 ± 27.4 cm/s). CONCLUSION: We describe significant hemodynamic effects of fistulas to the vertebral and internal mammary arteries. Doppler spectral analysis of the vertebral and internal mammary arteries should be integrated in ultrasound, especially in patients with cerebrovascular or cardiac symptoms.

Long-term follow-up after endovascular revascularisation for acute limb ischaemia--a retrospective single-centre cohort.

BACKGROUND: We evaluated the long-term outcome after endovascular revascularisation for acute limb ischaemia (ALI). PATIENTS AND METHODS: From a prospectively maintained database, 318 endovascular interventions for ALI were identified between 2004 and 2010. Event history and survival were analysed using the Kaplan-Meier method and Cox regression. Endpoints were target vessel revascularisation (TVR), non-target extremity revascularisation (NTER), amputation, major vascular events, coronary artery revascularisation and amputation-free survival. RESULTS: Follow-up data of 303 patients (mean age 68.5 ± 12.7 years, 40% female) were available. The mean follow-up time was 38.7 ± 26.2 months. TVR was performed in 40.1 ± 2.9% at 1 year and 66.5 ± 3.8% at 5 years. NTER at 1 and 5 years were 7.1 ± 1.5% and 29.2 ± 4%, respectively. The proportion of patients who needed major or minor amputation was 4.3 ± 1.2% after 1 year and 9 ± 2.1% after 5 years. Amputation-free survival at 1 year was 90.3 ± 1.8% and 74.8 ± 3.2% at 5 years. Coronary artery disease (HR 2.22, 95% CI 1.33 to 3.7, p = 0.002) and atrial fibrillation (HR 2.56, % CI 1.3 to 5.04, p = 0.007) were independently associated with a worse amputation-free survival. The cumulative proportion surviving one year following acute limb ischemia was 95.4 ± 1.2% and 79.7 ± 3.1% after 5 years. CONCLUSIONS: Long-term amputation-free survival after successful revascularisation for ALI is high; negative predictors are coronary artery disease and atrial fibrillation.

Misdiagnosis of plexiform neurofibroma as venous malformation in pediatric patients.

BACKGROUND: The aim of this study was to identify Magnetic Resonance Imaging (MRI) characteristics that reliably distinguish deep plexiform neurofibromas (PNFs) from venous malformations (VMs). METHODS: A database search was conducted for patients that were referred with a vascular anomaly but had a neurofibroma instead. Clinical and imaging features of patients with venous malformations as the most common referral diagnosis were compared to those with PNFs. The imaging features of deep PNFs recorded were: anatomical location, size, morphology, margins, signal intensity and post-contrast enhancement pattern. RESULTS: Ten patients with PNFs were identified. Five patients had adequate imaging. These five patients were included in our study. There were 3 female and 2 male patients ranging in age from 10 months to 21 years. Deep PNFs were located in the cervicofacial region (N.=3), lower extremity (N.=1) and back/flank region (N.=1). The most common clinical features of all these patients were palpable mass (N.=5) and pain (N.=4). The MRI features that distinguished VMs from deep PNFs were the serpiginous morphology, relatively intermediate T-2 signal intensity and peculiar enhancement pattern without fluid-fluid levels or phleboliths and nerve root involvement. The target sign can be regularly found in PNFs, but may be also present in VMs and other vascular lesions. CONCLUSIONS: Target signs, a typical sign of PNFs may be absent and can also be found in vascular anomalies, leading to confusion in diagnosis. PNFs can be reliably distinguished from VMs on MRI based on the above mentioned features.

Nitrous oxide/oxygen inhalation provides effective analgesia during the administration of tumescent local anaesthesia for endovenous laser ablation.

BACKGROUND: Tumescent anaesthesia (TA) is an important but sometimes very painful step during endovenous thermal ablation of incompetent veins. The aim of this study was to examine whether the use of fixed 50% nitrous oxide/oxygen mixture (N2O/O2), also called equimolar mixture of oxygen and nitrous oxide, reduces pain during the application of TA. PATIENTS AND METHODS: Patients undergoing endovenous laser ablation (EVLA) of incompetent saphenous veins were included. Thirty consecutive patients inhaled N2O/O2 during the application of TA. Thirty consecutive patients received TA alone (controls). Patients were asked to complete a questionnaire immediately after the intervention to assess satisfaction with the intervention and pain-levels during the different steps of the intervention (0=not at all, 10=very much). Adverse events during the treatment were monitored. RESULTS: 30 patients (14 men, mean age of 44 years) were included in the N2O/O2 group and 30 patients (9 men, mean age 48 years) were included in the control group. In the N2O/O2 group a significantly lower pain score was noted (mean 2.45 points, range 0-6) compared to the controls (mean 4.3 points, range 1-9, p<0.001). Overall, 64.5% of the patients were perfectly satisfied with the N2O/O2-Inhalation. Only 4 patients receiving N2O/O2 complained of adverse effects such as unpleasant loss of control (2 patients), headache (1 patient) and dizziness (1 patient). CONCLUSIONS: N2O/O2 is a safe and effective method to reduce pain during the application of tumescent anaesthesia for EVLA.

Risk Stratification of Patients with Peripheral Arterial Disease and Abdominal Aortic Aneurysm Using Aortic Augmentation Index.

BACKGROUND: Central augmentation index (cAIx) is an indicator for vascular stiffness. Obstructive and aneurysmatic vascular disease can affect pulse wave propagation and reflection, causing changes in central aortic pressures. AIM: To assess and compare cAIx in patients with peripheral arterial disease (PAD) and / or abdominal aortic aneurysm (AAA). METHODS: cAIx was assessed by radial applanation tonometry (Sphygmocor) in a total of 184 patients at a tertiary referral centre. Patients were grouped as having PAD only, AAA only, or both AAA and PAD. Differences in cAIx measurements between the three patient groups were tested by non-parametric tests and stepwise multivariate linear regression analysis to investigate associations with obstructive or aneurysmatic patterns of vascular disease. RESULTS: In the study sample of 184 patients, 130 had PAD only, 20 had AAA only, and 34 patients had both AAA and PAD. Mean cAIx (%) was 30.5 ± 8.2 across all patients. It was significantly higher in females (35.2 ± 6.1, n = 55) than males (28.4 ± 8.2, n = 129), and significantly higher in patients over 80 years of age (34.4 ± 6.9, n = 22) than in those under 80 years (30.0 ± 8.2, n = 162). Intergroup comparison revealed a significant difference in cAIx between the three patient groups (AAA: 27.3 ± 9.5; PAD: 31.4 ± 7.8; AAA & PAD: 28.8 ± 8.5). cAIx was significantly lower in patients with AAA, higher in patients with both AAA and PAD, and highest in patients with PAD only (beta = 0.21, p = 0.006). CONCLUSION: Non-invasive assessment of arterial stiffness in high-risk patients indicates that cAIx differs according to the pattern of vascular disease. Measurements revealed significantly higher cAIx values for patients with obstructive peripheral arterial disease than for patients with aneurysmatic disease.