Marc Husmann

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.

Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism

The Outpatient Bleeding Risk Index (OBRI) and the Kuijer, RIETE and Kearon scores are clinical prognostic scores for bleeding in patients receiving oral anticoagulants for venous thromboembolism (VTE). We prospectively compared the performance of these scores in elderly patients with VTE.

Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer The SWIss Venous ThromboEmbolism Registry (SWIVTER) II

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.

Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE).

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.

Magnetic resonance angiography in infrapopliteal arterial disease: prospective comparison of 1.5 and 3 Tesla magnetic resonance imaging.

Purpose:To prospectively determine the accuracy of 1.5 Tesla (T) and 3 T magnetic resonance angiography (MRA) versus digital subtraction angiography (DSA) in the depiction of infrageniculate arteries in patients with symptomatic peripheral arterial disease. Patients and Methods:A prospective 1.5 T, 3 T MRA, and DSA comparison was used to evaluate 360 vessel segments in 10 patients (15 limbs) with chronic symptomatic peripheral arterial disease. Selective DSA was performed within 30 days before both MRAs. The accuracy of 1.5 T and 3 T MRA was compared with DSA as the standard of reference by consensus agreement of 2 experienced readers. Signal-to-noise ratios (SNR) and signal-difference-to-noise ratios (SDNRs) were quantified. Results:No significant difference in overall image quality, sufficiency for diagnosis, depiction of arterial anatomy, motion artifacts, and venous overlap was found comparing 1.5 T with 3 T MRA (P > 0.05 by Wilcoxon signed rank and as by Cohen k test). Overall sensitivity of 1.5 and 3 T MRA for detection of significant arterial stenosis was 79% and 82%, and specificity was 87% and 87% for both modalities, respectively. Interobserver agreement was excellent k > 0.8, P < 0.05) for 1.5 T as well as for 3 T MRA. SNR and SDNR were significantly increased using the 3 T system (average increase: 36.5%, P < 0.032 by t test, and 38.5%, P < 0.037 respectively). Conclusions:Despite marked improvement of SDNR, 3 T MRA does not yet provide a significantly higher accuracy in diagnostic imaging of atherosclerotic lesions below the knee joint as compared with 1.5 T MRA.

MR Angiography of Infrapopliteal Arteries in Patients with Peripheral Arterial Occlusive Disease by Using Gadofosveset at 3.0 T: Diagnostic Accuracy Compared with Selective DSA

PURPOSE To prospectively compare the diagnostic accuracy of steady-state, high-spatial-resolution magnetic resonance (MR) angiography of the lower leg, performed with a blood pool contrast agent, with selective digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial disease. MATERIALS AND METHODS Local ethics committee approval and written informed consent were obtained. In a nonrandomized trial, selective DSA and MR angiography were performed at 3.0 T with a blood pool contrast agent on 22 calves in 20 patients (mean age, 69.4 years +/- 11.3 [standard deviation]), 16 men (mean age, 67.8 years +/- 12.4) and four women (mean age, 75.6 years +/- 3.6 years), to evaluate 352 arterial segments. DSA and MR angiography were performed within 24 hours of each other and directly compared by three experienced, blinded radiologists by using high-spatial-resolution steady-state MR angiograms. Consensus reading for both DSA and MR angiography served as the reference standard. RESULTS MR angiography was successful and occurred without serious adverse events in all patients. Seven significantly stenosed and 40 occluded segments were rated equally in both modalities. In three cases, the tibial arteries were shown to be occluded or significantly stenosed at DSA but appeared normal or significantly stenosed at MR angiography. The respective average segment sensitivity, specificity, and accuracy were 98.3% (59 of 60), 98% (113.7 of 116), and 98.1% (172.7 of 176) for DSA and 100% (60 of 60), 100% (116 of 116), and 100% (176 of 176) for MR angiography. Steady-state MR angiography was especially useful for the distal peroneal artery and the proximal anterior tibial artery. CONCLUSION MR angiography performed with blood pool agents has an accuracy comparable with that of selective DSA in the lower leg but with less risk involved. Steady-state imaging performed with blood pool agents facilitates evaluation of MR angiography of infrapopliteal arteries.

Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index : The SWIss Venous ThromboEmbolism Registry (SWIVTER)

A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38-8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76-44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63-0.81) than sPESI alone (HR 0.63, 95% CI 0.57-0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

The Influence of Abdominal Pressure on Lower Extremity Venous Pressure and Hemodynamics: A Human In-vivo Model Simulating the Effect of Abdominal Obesity

OBJECTIVE To demonstrate that abdominal pressure impacts venous flow and pressure characteristics. METHODS Venous pressure at the femoral vein was measured in 6 non-obese subjects (mean BMI 22 ± 2 kg/m(2)) that were exposed to a circumferential cuff placed around the abdominal trunk and inflated to 20 and 40 mmHg. In a second step non-obese subjects (n = 10, BMI 21.8 ± 1.8 kg/m(2)) exposed to this cuff compression were studied for duplexsonographic parameters at the femoral vein. Duplexsonographic results were compared to subjects with abdominal obesity (n = 22, BMI 36.2 ± 5.9 kg/m(2)) in whom duplexsonographic parameters at the femoral vein were studied without cuff compression. RESULTS Intravenous pressure increased with pressure application in all participants (p = 0.0025). Duplex examination of 10 non-obese subjects revealed increasing venous diameter (p < 0.0001) and decreasing venous peak and mean velocity (all p < 0.0001) when cuff pressure was applied. Duplex parameters with cuff pressure application of 20 and 40 mmHg respectively, were similar to those in obese subjects that were studied without pressure application. CONCLUSIONS External abdominal pressure application creates venous stasis in lower limbs. Results of this study indicate that abdominal obesity might induce resistance to venous backflow from the lower limbs.

Predictors of in-hospital mortality in elderly patients with acute venous thrombo-embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER)

AIMS Although acute venous thrombo-embolism (VTE) often afflicts patients with advanced age, the predictors of in-hospital mortality for elderly VTE patients are unknown. METHODS AND RESULTS Among 1247 consecutive patients with acute VTE from the prospective SWIss Venous ThromboEmbolism Registry (SWIVTER), 644 (52%) were elderly (≥65 years of age). In comparison to younger patients, the elderly more often had pulmonary embolism (PE) (60 vs. 42%; P< 0.001), cancer (30 vs. 20%; P< 0.001), chronic lung disease (14 vs. 8%; P= 0.001), and congestive heart failure (12 vs. 2%; P< 0.001). Elderly VTE patients were more often hospitalized (75 vs. 52%; P< 0.001), and there was no difference in the use of thrombolysis, catheter intervention, or surgical embolectomy between the elderly and younger PE patients (5 vs. 6%; P= 0.54), despite a trend towards a higher rate of massive PE in the elderly (8 vs. 4%; P= 0.07). The overall in-hospital mortality rate was 6.6% in the elderly vs. 3.2% in the younger VTE patients (P= 0.033). Cancer was associated with in-hospital death both in the elderly [hazard ratio (HR) 4.91, 95% confidence interval (CI) 2.32-10.38; P< 0.001] and in the younger patients (HR 4.90, 95% CI 1.37-17.59; P= 0.015); massive PE was a predictor of in-hospital death in the elderly only (HR 3.77, 95% CI 1.63-8.74; P= 0.002). CONCLUSION Elderly patients had more serious VTE than younger patients, and massive PE was particularly life-threatening in the elderly.

Successful lower extremity angioplasty improves brachial artery flow-mediated dilation in patients with peripheral arterial disease.

INTRODUCTION Peripheral arterial disease (PAD) is associated with systemic impaired flow-mediated dilation (FMD) and increased risk for cardiovascular events. Decreased FMD may be caused by a decrease in arterial shear stress due to claudication and inflammation due to muscle ischemia and reperfusion. We assumed that endovascular revascularization of lower limb arterial obstructions ameliorates FMD and lowers inflammation through improvement of peripheral perfusion. METHODS The study was a prospective, open, randomized, controlled, single-center follow-up evaluation assessing the effect of endovascular revascularization on brachial artery reactivity (FMD) measured by ultrasound, white blood cell (WBC) count, high-sensitive C-reactive protein (hs-CRP), and fibrinogen. We investigated 33 patients (23 men) with chronic and stable PAD (Rutherford 2 to 3) due to femoropopliteal obstruction. Variables were assessed at baseline and after 4 weeks in 17 patients (group A) who underwent endovascular revascularization and best medical treatment, and in 16 patients (group B) who received best medical treatment only. RESULTS FMD did not differ between group A and B (4.96% +/- 1.86% vs 4.60% +/- 2.95%; P = .87) at baseline. It significantly improved after revascularization in group A (6.44% +/- 2.88%; P = .02) compared with group B at 4 weeks of follow-up (4.53% +/- 3.17%; P = .92), where it remained unchanged. The baseline ankle-brachial index (ABI) was similar for group A and B (0.63 +/- 0.15 vs 0.66 +/- 0.10; P = .36). At 4 weeks of follow-up, ABI was significantly increased in group A (1.05 +/- 0.15; P = .0004) but remained unchanged in group B (0.62 +/- 0.1). WBC counts of the two groups were comparable at baseline (group A: 7.6 +/- 2.26 x 10(6)/mL and group B: 7.8 +/- 2.02 x 10(6)/mL, P = .81). In group A, the leukocyte count significantly decreased after angioplasty from 7.6 +/- 2.26 to 6.89 +/- 1.35 x 10(6)/mL (P = .03). For group B, WBC count did not differ significantly compared with baseline (7.76 +/- 2.64 x 10(6)/mL; P = .94). No effects were observed on hs-CRP or fibrinogen from endovascular therapy. CONCLUSION Endovascular revascularization with reestablishment of peripheral arterial perfusion improves FMD and reduces WBC count in patients with claudication. Revascularization may therefore have clinical implications beyond relief of symptoms, for example, reducing oxidative stress caused by repeated muscle ischemia or increased shear stress due to improved ambulatory activity.