Beatrice Amann-Vesti

Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes

AIMS Inflammation plays a key role in acute coronary syndromes (ACS). Toll-like receptors (TLR) on leucocytes mediate inflammation and immune responses. We characterized leucocytes and TLR expression within coronary thrombi and compared cytokine levels from the site of coronary occlusion with aortic blood (AB) in ACS patients. METHODS AND RESULTS In 18 ACS patients, thrombi were collected by aspiration during primary percutaneous coronary intervention. Thrombi and AB from these patients as well as AB from 10 age-matched controls without coronary artery disease were assessed by FACS analysis for cellular distribution and TLR expression. For further discrimination of ACS specificity, seven non-coronary intravascular thrombi and eight thrombi generated in vitro were analysed. In 17 additional patients, cytokine levels were determined in blood samples from the site of coronary occlusion under distal occlusion and compared with AB. In coronary thrombi from ACS, the percentage of monocytes related to the total leucocyte count was greater than in AB (47 vs. 20%, P = 0.0002). In thrombi, TLR-4 and TLR-2 were overexpressed on CD14-labelled monocytes, and TLR-2 was increased on CD66b-labelled granulocytes, in comparison with leucocytes in AB. In contrast, in vitro and non-coronary thrombi exhibited no overexpression of TLR-4. Local blood samples taken under distal occlusion revealed elevated concentrations of chemokines (IL-8, MCP-1, eotaxin, MIP-1alpha, and IP-10) and cytokines (IL-1ra, IL-6, IL-7, IL-12, IL-17, IFN-alpha, and granulocyte-macrophage colony-stimulating factor) regulating both innate and adaptive immunity (all P < 0.05). CONCLUSION In ACS patients, monocytes accumulate within thrombi and specifically overexpress TLR-4. Together with the local expression patterns of chemokines and cytokines, the increase of TLR-4 reflects a concerted activation of this inflammatory pathway at the site of coronary occlusion in ACS.

Impact of obesity on venous hemodynamics of the lower limbs

BACKGROUND Obesity is a risk factor for chronic venous insufficiency and venous thromboembolism. The aim of this study was to compare venous flow parameters of the lower limbs assessed by duplex ultrasound scanning in obese and nonobese individuals according to body mass index (BMI). METHODS Venous hemodynamics were studied in a prospective cohort study in nonobese (BMI <25 kg/m(2)) and obese individuals (BMI >30 kg/m(2)). Diameter, flow volume, peak, mean, and minimum velocities were assessed. RESULTS The study examined 36 limbs in 23 nonobese individuals and 44 limbs in 22 obese individuals. The diameter of the femoral vein was significantly greater in obese (8.5 +/- 2.2 mm) vs nonobese (7.1 +/- 1.6 mm; P = .0009) limbs. Venous peak and minimum velocities differed between nonobese and obese individuals (14.8 +/- 7.2 vs 10.8 +/- 4.8 cm/s [P = .0071] and 4.0 +/- 3.6 vs 1.7 +/- 6.3 cm/s [P = .056]). Calculation of venous amplitude and shear stress showed significantly higher values in nonobese vs obese (18.8 +/- 9.4 vs 12.5 +/- 9.3 cm/s [P = .003] and 2.13 +/- 2.2 dyn/cm(2) vs 1.6 +/- 2.7 dyn/cm(2) [P = .03]). Spearman rank correlation revealed a significant inverse correlation between waist-to-hip ratios and waist circumference and venous peak velocity, mean velocity, velocities amplitude (peak velocity-minimum velocity), and shear stress. CONCLUSION Lower limb venous flow parameters differ significantly between healthy obese and nonobese individuals. These findings support the mechanical role of abdominal adipose tissue potentially leading to elevated risk for both venous thromboembolism and chronic venous insufficiency.

Predictive value of naitfold capillaroscopy in patients with Raynaud’s phenomenon

The objective of this study was to evaluate the long-term follow-up of patients with Raynaud’s phenomenon (RP) and pathological nailfold capillaroscopy (NC) in order to analyse the predictive value of specific features of capillaroscopy for the development of a connective tissue disease (CTD). From 1992 to 2002, NC alone or combined with fluorescence videomicroscopy with sodium fluorescein (NaF) was performed in 1024 consecutive patients because of RP. We analysed the follow-up and pathological features of NC in all patients who had neither clinical nor serological signs of a CTD at the time of NC. Of 308 patients with neither serological findings nor clinical signs of CTD but with RP and pathological features in NC suspicious for CTD, follow-up data were available for 133 patients. An additional NaF test had been performed in 51 (38.4%) patients. After a mean follow-up of 6.5 years (range: 1–15 years), 109 patients had developed a CTD and 24 patients did not show any clinical signs or serological markers for a CTD after a mean follow-up of 8.5 years (range: 2–15 years). There were no differences in age, duration of RP or of follow-up in patients who developed a CTD compared to patients who did not. Significantly more giant capillaries (p=0.0001), avascular fields (p=0.02) and irregular architecture (p=0.0001) had been observed in patients who had developed a CTD during the follow-up of 6.5 years. The presence of giant capillaries, avascular fields and irregular architecture of nailfold capillaries is predictive for the development of a CTD in patients with RP.

Martorell Hypertensive Ischemic Leg Ulcer A Model of Ischemic Subcutaneous Arteriolosclerosis

OBJECTIVES To better define the diagnosis and treatment of Martorell hypertensive ischemic leg ulcer (HYTILU) and to compare Martorell HYTILU with calciphylaxis (calcific uremic arteriolopathy) and nonuremic forms of calciphylaxis. DESIGN Retrospective study from 1999 through 2007. SETTING Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. PARTICIPANTS Of 330 patients with leg ulcers, 31 had a clinical diagnosis of Martorell HYTILU confirmed by dermatopathologic examination. MAIN OUTCOME MEASURES Clinical features, suspected diagnosis at initial presentation, cardiovascular risk factors, findings from vascular examination and histologic analysis, specific medical and surgical management, and outcome. RESULTS Of the 31 patients, all presented with 1 or multiple painful necrotic skin ulcers on the laterodorsal part of the leg, with bilateral involvement in 16 of 31 cases (52%), and 16 were referred with suspected pyoderma gangrenosum. All patients had arterial hypertension, and 18 (58%) had diabetes. All patients had subcutaneous stenotic arteriolosclerosis on histologic analysis, with medial calcification in 22 of 31 of cases (71%). Martorell HYTILU, calciphylaxis, and nonuremic forms of calciphylaxis shared identical histologic features. Of the 31 patients, 29 (94%) were successfully treated with surgical debridement and split-thickness skin grafting. Three patients (9%) died of sepsis, 2 of whom were undergoing immunosuppressive treatment for wrongly diagnosed pyoderma gangrenosum. CONCLUSIONS Ischemic subcutaneous arteriolosclerosis is the hallmark of Martorell HYTILU, calciphylaxis, and the nonuremic forms of calciphylaxis. All patients are hypertensive and approximately 60% are diabetic. Martorell HYTILU can easily be confused with pyoderma gangrenosum, which can be detrimental, since the 2 diseases require a completely different treatment strategy.

Late acute thrombotic occlusion after endovascular brachytherapy and stenting of femoropopliteal arteries

OBJECTIVES The aim of this article is to underline the importance of this complication after endovascular brachytherapy (EVBT) and intravascular stenting of the femoropopliteal arteries occurring in a running randomized trial. BACKGROUND Endovascular brachytherapy has been proposed as a promising treatment modality to reduce restenosis after angioplasty. However, the phenomenon of late acute thrombotic occlusion (LATO) in patients receiving EVBT after stenting is of major concern. METHODS In an ongoing prospective multicenter trial, patients were randomized to undergo EVBT (iridium 192; 14 Gy at a depth of the radius of the vessel +2 mm) after percutaneous recanalization of femoropopliteal obstructions. Of the 204 patients who completed the six months follow-up, 94 were randomized to EVBT. RESULTS Late acute thrombotic occlusion occurred exclusively in 6 of 22 patients (27%) receiving EVBT after intravascular stenting and always in concomitance with reduction of antithrombotic drug prevention (clopidogrel). Conversely, none of the 13 patients with stents and without EVBT (0%; p < 0.05) and none of the 72 patients (0%; p < 0.01) undergoing EVBT after simple balloon angioplasty presented LATO. CONCLUSIONS Late thrombotic occlusion occurs not only in patients undergoing EVBT after percutaneous coronary recanalization but also after stenting of the femoropopliteal arteries and may compromise the benefits of endovascular radiation. The fact that all our cases with LATO occurred concomitantly with stopping clopidogrel may indicate a possible rebound mechanism. An intensive and prolonged antithrombotic prevention is probably indicated in these patients.

Obstructive sleep apnea in patients with abdominal aortic aneurysms: highly prevalent and associated with aneurysm expansion.

RATIONALE Abdominal aortic aneurysms (AAA) are associated with life-threatening complications. The likelihood that an AAA will rupture is influenced by the aneurysm diameter and its expansion rate; reasons for rapid expansion are largely unknown. OBJECTIVES To determine the prevalence of obstructive sleep apnea (OSA) in patients with AAA, and investigate a possible association between OSA and rate of AAA expansion. METHODS A total of 127 patients (11 females), included in an AAA surveillance program, agreed to participate and underwent a sleep study. Annual AAA expansion was determined retrospectively from available ultrasound measurements. OSA was characterized using both oxygen desaturation index (ODI) and apnea-hypopnea index (AHI). Univariate and multivariate analysis was performed to assess the effect of OSA severity on AAA expansion. MEASUREMENTS AND MAIN RESULTS Mean age was 67.9 (SD, 6) years. Median interval between the first and last AAA measurements was 18 (range, 2-113) months. An ODI or AHI of greater than 10 was found in 40.5% and 41.5% of the patients, respectively. Patients with an ODI greater than 30 (n = 12) had a significantly faster median yearly AAA expansion rate (2.9; quartiles 2/5.7 mm/y) than patients with an ODI 0-5 (n = 47; 1.2; quartiles 0/3.1 mm/y) or 6-15 (n = 43; 1.3; quartiles 0/2.7 mm/y) (P < 0.05). In multivariate regression analysis, controlling for cardiovascular risk factors and medications, ODI greater than 30 remained an independent risk factor for AAA expansion. CONCLUSIONS In patients with AAA, OSA is highly prevalent. Severe OSA may be a causal factor for faster AAA expansion, but this needs to be proved in a randomized controlled intervention trial.

Flow Impairment during Protected Carotid Artery Stenting: Impact of Filter Device Design

Purpose: To investigate the impact of filter design on blood flow impairment in the internal carotid artery (ICA) among patients undergoing carotid artery stenting (CAS) using filtertype emboli protection devices (EPD). Methods: Between July 2003 and March 2007, 115 filter-protected CAS procedures were performed at an academic institution in 107 consecutive patients (78 men; mean age 68 years, range 38–87). The Angioguard, FilterWire EZ, and Spider filters were used in 68 (59%), 32 (28%), and 15 (13%) of cases, respectively. Patient characteristics, procedural and angiographic data, and outcomes were prospectively entered into an electronic database and reviewed retrospectively along with all angiograms. Results: Flow impairment while the filter was in place was observed in 25 (22%) cases. The presumptive reason of flow impairment was filter obstruction in 21 (18%) instances and flow-limiting spasm at the level of the filter in 4 (4%). In all cases, flow was restored after retrieval of the filter. Flow obstruction in the ICA occurred more frequently with Angioguard (22/68; 32.3%) than with FilterWire EZ (2/32; 6.2%) or Spider (1/15; 6.7%; p=0.004). No flow occurred in 13 (19%) procedures, all of them protected with Angioguard; no patient treated with other devices experienced this event (p=0.007). Two (8.0%) strokes occurred in procedures associated with flow impairment, while 1 (1.1%) event was observed in the presence of preserved flow throughout the intervention (p=0.11). Conclusion: Flow impairment in the ICA during filter-based CAS is common and related to the type of filter used.

Microcirculation abnormalities in patients with fibromyalgia – measured by capillary microscopy and laser fluxmetry

This unblinded preliminary case-control study was done to demonstrate functional and structural changes in the microcirculation of patients with primary fibromyalgia (FM). We studied 10 women (54.0 ± 3.7 years of age) with FM diagnosed in accordance with the classification criteria of the American College of Rheumatology, and controls in three groups (n = 10 in each group) – age-matched women who were healthy or who had rheumatoid arthritis or systemic scleroderma (SSc). All 40 subjects were tested within a 5-week period by the same investigators, using two noninvasive methods, laser fluxmetry and capillary microscopy. The FM patients were compared with the healthy controls (negative controls) and with rheumatoid arthritis patients and SSc patients (positive controls). FM patients had fewer capillaries in the nail fold (P < 0.001) and significantly more capillary dilatations (P < 0.05) and irregular formations (P < 0.01) than the healthy controls. Interestingly, the peripheral blood flow in FM patients was much less (P < 0.001) than in healthy controls but did not differ from that of SSc patients (P = 0.73). The data suggest that functional disturbances of microcirculation are present in FM patients and that morphological abnormalities may also influence their microcirculation.

Immediate and long-term outcome of upper extremity balloon angioplasty in giant cell arteritis.

Purpose: To review the immediate and long-term results of subclavian, axillary, and brachial artery balloon angioplasty (PTA) in giant cell arteritis (GCA). Case Reports: Four patients (3 men; mean age 65±8.9 years) with upper limb claudication due to GCA underwent PTA for 2 stenoses and 1 occlusion of the subclavian artery, 6 stenoses and 2 occlusions of the axillary artery, and 2 stenoses of the brachial artery. Patients received steroids prior to the intervention, and steroid treatment was continued for at least 2 years. All procedures were performed successfully with no residual stenosis. At follow-up after 2 years (n=2), 5 years (n = 1), and 10 years (n = 1), no significant recurrent stenoses were detected by duplex scanning. Conclusions: PTA is a safe and effective therapy for stenotic lesions and occlusions of the upper limb arteries due to GCA. The long-term results seem to benefit from postprocedural therapy with steroids and aspirin.

Non-coronary atherosclerosis

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