Gerald Hackl

Endothelial dysfunction and brachial intima-media thickness: long term cardiovascular risk with claudication related to peripheral arterial disease: a prospective analysis.

Objective Endothelial dysfunction plays a key role in the development, progression, and clinical manifestation of atherosclerosis, and in symptomatic peripheral arterial disease, endothelial dysfunction and enlarged intima-media thickness might be associated with increased cardiovascular risk. Flow-mediated dilatation and serologic parameters are used to evaluate individual endothelial function. Brachial intima-media thickness, a less recognized parameter of cardiovascular risk, is independently associated with coronary artery disease. The aim of this study was to evaluate the prognostic value of ultrasound and serologic parameters of endothelial function in relation to cardiovascular mortality in peripheral arterial disease. Design monocentric, prospective cohort study. Methods Flow mediated dilatation and brachial intima-media thickness were assessed in 184 (124 male) patients with peripheral arterial disease (Rutherford stages 2–3). Serologic parameters of endothelial function included asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine. Cardiovascular events were recorded during a follow-up of 99.1±11.1 months. Subjects who died of noncardiovascular causes were excluded from further analysis. Results Eighty-two patients (44.6%) died during follow-up after a mean duration of 49.7±28.3 months. There were 49 cardiovascular deaths (59.8%) and 33 other deaths (40.2%). Flow mediated dilatation was associated with cardiovascular death [1.17% (0.0, 4.3) vs. 4.1% (1.2, 6.4), p<0.001]. Intima-media thickness was greater in patients who succumbed to cardiovascular disease [0.37 mm (0.30, 0.41)] than in survivors [0.21 mm (0.15, 0.38), p<0.001]. Brachial intima-media thickness above 0.345 mm was most predictive of cardiovascular death, with sensitivity and specificity values of 0.714 and 0.657, respectively (p<0.001). Furthermore, ADMA levels above 0.745 µmol/l and SDMA levels above 0.825 µmol/l were significantly associated with cardiovascular death (p<0.001 and 0.030). Conclusion In symptomatic peripheral arterial disease, decreased flow mediated dilatation, enlarged intima-media thickness, and elevated levels of ADMA and SDMA were associated with increased cardiovascular risk.

Exoseal for puncture site closure after antegrade procedures in peripheral arterial disease patients.

PURPOSE Exoseal is a vascular clo-sure device consisting of a plug applier and a bio-absorbent polyglycolic acid plug available in sizes 5 F, 6 F, and 7 F. In this study, we aimed to evaluate the effectiveness and safety of the Exoseal vascular closure device (Cordis Corporation, Bridgewater, New Jersey, USA) for puncture site closure after antegrade endovascular procedures in peripheral arterial occlusive disease (PAOD) patients. MATERIALS AND METHODS In this retrospective study, a total of 168 consecutive patients who underwent an interventional procedure due to PAOD, were included. In each case, an antegrade peripheral endovascular procedure was performed via the common femoral artery using the Seldinger technique, and Exoseal 5 F, 6 F, or 7 F was used for access site closure. The primary endpoint was a technically successful application of Exoseal. All complications at the access site within 24 hours were registered as a secondary endpoint. RESULTS In a group of 168 patients (64.9% men, average age 71.9±11.9 years), the technical application of Exoseal was successful in 166 patients (98.8%). Within the first 24 hours after the procedure, 12 complications (7.2%) were recorded including, three pseudoaneurysms (1.8%) and nine hematomas (5.4%). None of the complications required surgical intervention. CONCLUSION Exoseal is a safe and effective device with high technical success and acceptable complication rates for access site closure after antegrade peripheral endovascular procedures.

Elevated Blood Urea Nitrogen is Associated With Critical Limb Ischemia in Peripheral Arterial Disease Patients.

AbstractAs renal function is often impaired in atherosclerosis patients, accelerating atherosclerosis per se and creating a vicious cycle, we investigated the association of blood urea nitrogen (BUN) and critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients.Our cross-sectional study included 1521 PAOD patients, with normal and impaired renal function treated at our institution from 2005 to 2010. Patients on renal replacement therapy were excluded. The cohort was divided into tertiles according to the serum BUN levels. An optimal cutoff value for the continuous BUN was calculated by applying a receiver-operating curve analysis to discriminate between CLI and non-CLI.In our cohort, CLI increased significantly with an increase in BUN (13.1% in the first tertile, 18.7% in the second tertile, 29.0% in the third tertile, P for trend <0.001). A BUN of 17.7 mg/dL was identified as an optimal cutoff. Accordingly, there were 2 groups of patients: 636 patients with BUN ⩽ 17.7 and 885 patients with BUN > 17.7. CLI was more frequent in BUN > 17.7 patients (342 [38.6%]) than in BUN ⩽ 17.7 patients (134 [21.1%]) (P < 0.001); the same applied to prior myocardial infarction (45 [5.1%] vs 15 [2.4%], P = 0.007) and congestive heart failure (86 [9.7%] vs 31 [4.9%], P < 0.001). A BUN > 17.7 was associated with an odds ratio of 1.6 (95% confidence interval: 1.3–1.9, P < 0.001) for CLI even after the adjustment for other established vascular risk factors such as age ≥75 and type 2 diabetes.An increased BUN is significantly associated with a high risk for CLI and other vascular endpoints. The BUN is an easily determinable, broadly available, and inexpensive marker that could be used to identify patients at high risk for vascular endpoints.

Successful Retrieval of an Embolized Vascular Closure Device (Angio-Seal®) After Peripheral Angioplasty

A 55-year-old male with peripheral arterial disease underwent angioplasty of the right lower limb arteries via antegrade femoral access. Angio-Seal® closure device was used to treat the puncture site, whereby the intravascular sealing anchor accidentally embolized into the malleolar region of the right posterior tibial artery. Successful retrieval of the anchor was accomplished by a SpiderFX embolic protection device. This technique may be a useful approach to retrieve embolized foreign bodies via endovascular access.

Changes in lipid metabolism and extension of venous thromboembolism.

Background/Aims: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common diseases with a vast number of acquired and congenital risk factors. Disorders of the lipid metabolism are not established risk factors for venous thromboembolism (VTE) so far. However, in recent literature, associations between VTE and the metabolic syndrome, especially with elevated lipid parameters, have been described. The aim of our study was to investigate the association between the extension of VTE and changes in the lipid profile. Methods: We included 178 VTE patients in our study; 59 patients had isolated PE, 39 patients had isolated DVT of the leg and 80 patients had both (DVT and PE). Concerning PE, we distinguished between massive and submassive PE. We evaluated plasma lipids and lipoproteins in PE and DVT patients as well as in massive and submassive PE patients. Results: PE patients had higher levels of plasma triglycerides [median (interquartile range): 162 (109-254) vs. 136.5 (96.5-162) mg/dl, p = 0.047] and lower levels of high-density lipoprotein cholesterol (HDL-C; 52.1 ± 17.2 vs. 63.9 ± 22.7 mg/dl, p = 0.004) than DVT patients. Furthermore, PE patients were significantly older than DVT patients (59.6 ± 16.9 vs. 52.2 ± 15.5 years, p = 0.02). We were not able to find differences in lipid parameters in patients with massive PE compared to those with submassive PE. However, patients with massive PE were more obese than patients with submassive PE (body mass index 29.1 ± 4.6 vs. 26.9 ± 4.9, p = 0.012). Conclusions: Lipid parameters and lipoproteins differ between DVT and PE patients. PE patients had higher triglyceride and lower HDL-C levels compared with DVT patients.

Auricular vagal nerve stimulation in peripheral arterial disease patients

BACKGROUND Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. PATIENTS AND METHODS In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). RESULTS There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128-236] meters to 345 [95 % CI 227-463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109-210] meters to 268 [95 % CI 182-366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. CONCLUSIONS Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for PAD patients.

Calculation of HAS-BLED Score Is Useful for Early Identification of Venous Thromboembolism Patients at High Risk for Major Bleeding Events: A Prospective Outpatients Cohort Study

Abstract The aim of this study was prospective evaluation of the performance of the HAS‐BLED score in predicting major bleeding complications in a real‐world outpatient cohort, during long‐term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long‐term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS‐BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS‐BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96‐692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87‐5.85, p = 0.091) when compared with patients with a HAS‐BLED score < 3.This indicates that a HAS‐BLED score ≥ 3 allows for identification of patients with VTE on long‐term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.

Waterhouse-Friderichsen syndrome due to Neisseria meningitidis infection in a young adult with thrombotic microangiopathy and eculizumab treatment: case report and review of management

Dear Editor, Recently, Alashkar et al. provided comprehensive data on the serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria who were chronically treated with the terminal complement inhibitor eculizumab [1]. As immunological response to meningococcal vaccine varies widely in this cohort from 48% for serotype W to 87% for serotype C, the author recommend monitoring serologic response to meningococcal vaccination after 6 months and to immediately re-vaccinate patients with nonprotective titers. Importantly, they also observed an impaired serological response in patients with concomitant immunosuppressive therapy. We here report the case of a 22-year-old patient suffering from systemic lupus erythematosus (SLE) with thrombotic microangiopathy (TMA) who developed a WaterhouseFriderichsen syndrome due toNeisseria meningitidis infection under chronic eculizumab treatment despite previous meningococcal vaccination. The patient had suffered from SLE since the age of 12 years. In April 2015, he developed TMA with acute renal failure AKI criteria 3 refractory to treatment with corticosteroids, cyclophosphamide, and plasmapheresis. Therefore, eculizumab was started with a parallel antibiotic prophylaxis with ciprofloxacin. In March 2016, the patient was vaccinated against Neisseria meningitidis serotype B and C which account for the most cases of meningococcal infections in Austria [2]. Three months after vaccination and 1 month after stopping ciprofloxacin, the patient was referred to the Intensive Care Unit of our hospital with septic shock, acute-on-chronic renal failure, and severe acute respiratory distress syndrome necessitating a high-dose norepinephrine treatment with corticosteroids, continuous renal replacement therapy, invasive mechanical ventilation, and extracorporeal lung assistance with a blood flow of 4 L/min to provide adequate oxygenation. Moreover, the patient had disseminated intravascular coagulation with thrombocytopenia (nadir of 15 g/L), severe hemorrhagic diathesis, purpura fulminans, and petechial bleedings in both lungs. Laboratory analysis showed leukocytosis of 20.1 g/L, a procalcitonin level of 789 ng/mL (0–0.5), and a C-reactive protein of 426 mg/L (0–5), respectively. Thus, the patient had all symptoms of fulminant sepsis syndrome. Indeed, blood cultures revealed meningococcal infection with Neisseria meningitidis serotype W135 as a cause for the Waterhouse-Friderichsen syndrome. The patient, who slowly recovered under antibiotic treatment with piperacillin and ceftriaxone, was dismissed from Intensive Care Unit after 18 days and discharged from our hospital after 48 days. Analysis of serological response to meningococcal vaccination revealed non-protective titers. He promptly received both meningococcal re-vaccination with a tetravalent conjugate vaccine and antibiotic prophylaxis with ciprofloxacin, but ultimately, the treatment with eculizumab was halted due to the near-fatal meningococcal infection. Taken together, this case report re-emphasizes the occurrence of rare Neisseria serotypes in patients under chronic eculizumab treatment and thus strongly argues for the use polyvalent conjugate vaccine covering meningococcal strains A, C, W, Y, and B [3–5]. Moreover, we completely agree with Alashkar F et al. and add further evidence that monitoring * Philipp Eller philipp.eller@medunigraz.at

Risk Factors for Puncture Site Complications After Endovascular Procedures in Patients With Peripheral Arterial Disease

Objective: To compare femoral access site closure techniques and to highlight risk factors for puncture site complications after lower extremity endovascular procedures. Methods: This retrospective study included 787 patients. Procedures were performed according to a standardized protocol. Puncture site complications within 24 hours were regarded as study end points. Results: Ninety (11.5%) puncture site complications were registered. Conventional manual compression (n = 87, 11.1%) was significantly associated with puncture site complications (odds ratio [OR] 2.08, P = .03). Body mass index > 25 kg/m2 (OR 0.54, P = .01) and prothrombin time > 70% (OR 0.38, P = .04) were protective. All bleeding occurred in procedures >45 minutes. Blood pressure >200 mm Hg and below the knee (BTK) procedures were strong predictors for access site complications (OR 4.21, P = .01 and OR 3.33, P = .02). Conclusions: We observed an inferiority of conventional manual compression. Age, procedure duration > 45 minutes, BTK procedures, uncontrolled hypertension, and impaired coagulation were risk factors.

Graz Critical Limb Ischemia Score: A Risk Score for Critical Limb Ischemia in Peripheral Arterial Occlusive Disease.

AbstractCritical limb ischemia (CLI), a frequently encountered disorder, is associated with a high rate of limb amputation and mortality. To identify patients at high risk for CLI, we developed a simple risk score for peripheral arterial occlusive disease (PAOD).In our cross-sectional study, we first evaluated 1000 consecutive PAOD patients treated at our institution from 2005 to 2007, documenting clinical symptoms, comorbidities, and concomitant medication. We calculated odds ratios (OR) in a binary logistic regression model to find possible risk factors for CLI. We then verified the score in a second step that included the 1124 PAOD patients we treated between 2007 and 2011.In the first patient group, the greatest risk factors for CLI were age ≥75 years (OR 2.0), type 2 diabetes (OR 3.1), prior myocardial infarction (OR 2.5), and therapy with low molecular weight heparins (2.8). We scored 1 point for each of those conditions. One point was given for age between 65 and 75 years (OR 1.6) as well as for therapy with cardiac glycosides (OR 1.9) or loop diuretic therapy (OR 1.5). As statin therapy was protective for CLI with an OR of 0.5, we subtracted 1 point for those patients.In the second group, we could prove that frequency of CLI was significantly higher in patients with a high CLI score. The score correlated well with inflammatory parameters (c-reactive protein and fibrinogen). We were also able to define 3 different risk groups for low (score −1 to 1), intermediate (score 2–4), and high CLI risk (score >4).We developed a simple risk stratification scheme that is based on conditions that can be easily assessed from the medical history, without any laboratory parameters. This score should help to identify PAOD patients at high risk for CLI.