Torsten Willenberg

Fixed low-dose ultrasound-assisted catheter-directed thrombolysis for intermediate- and high-risk pulmonary embolism

AIMSnNo standardized local thrombolysis regimen exists for the treatment of pulmonary embolism (PE). We retrospectively investigated efficacy and safety of fixed low-dose ultrasound-assisted catheter-directed thrombolysis (USAT) for intermediate- and high-risk PE.nnnMETHODS AND RESULTSnFifty-two patients (65 ± 14 years) of whom 14 had high-risk PE (troponin positive in all) and 38 intermediate-risk PE (troponin positive in 91%) were treated with intravenous unfractionated heparin and USAT using 10 mg of recombinant tissue plasminogen activator per device over the course of 15 h. Bilateral USAT was performed in 83% of patients. During 3-month follow-up, two [3.8%; 95% confidence interval (CI) 0.5-13%] patients died (one from cardiogenic shock and one from recurrent PE). Major non-fatal bleeding occurred in two (3.8%; 95% CI, 0.5-13%) patients: one intrathoracic bleeding after cardiopulmonary resuscitation requiring transfusion, one intrapulmonary bleeding requiring lobectomy. Mean pulmonary artery pressure decreased from 37 ± 9 mmHg at baseline to 25 ± 8 mmHg at 15 h (P < 0.001) and cardiac index increased from 2.0 ± 0.7 to 2.7 ± 0.9 L/min/m(2) (P < 0.001). Echocardiographic right-to-left ventricular end-diastolic dimension ratio decreased from 1.42 ± 0.21 at baseline to 1.06 ± 0.23 at 24 h (n = 21; P < 0.001). The greatest haemodynamic benefit from USAT was found in patients with high-risk PE and in those with symptom duration < 14 days.nnnCONCLUSIONnA standardized catheter intervention approach using fixed low-dose USAT for the treatment of intermediate- and high-risk PE was associated with rapid improvement in haemodynamic parameters and low rates of bleeding complications and mortality.

In search of optimal compression therapy for venous leg ulcers: A meta-analysis of studies comparing divers bandages with specifically designed stockings

OBJECTIVEnIn search of an optimal compression therapy for venous leg ulcers, a systematic review and meta-analysis was performed of randomized controlled trials (RCT) comparing compression systems based on stockings (MCS) with divers bandages.nnnMETHODSnRCT were retrieved from six sources and reviewed independently. The primary endpoint, completion of healing within a defined time frame, and the secondary endpoints, time to healing, and pain were entered into a meta-analysis using the tools of the Cochrane Collaboration. Additional subjective endpoints were summarized.nnnRESULTSnEight RCT (published 1985-2008) fulfilled the predefined criteria. Data presentation was adequate and showed moderate heterogeneity. The studies included 692 patients (21-178/study, mean age 61 years, 56% women). Analyzed were 688 ulcerated legs, present for 1 week to 9 years, sizing 1 to 210 cm(2). The observation period ranged from 12 to 78 weeks. Patient and ulcer characteristics were evenly distributed in three studies, favored the stocking groups in four, and the bandage group in one. Data on the pressure exerted by stockings and bandages were reported in seven and two studies, amounting to 31-56 and 27-49 mm Hg, respectively. The proportion of ulcers healed was greater with stockings than with bandages (62.7% vs 46.6%; P < .00001). The average time to healing (seven studies, 535 patients) was 3 weeks shorter with stockings (P = .0002). In no study performed bandages better than MCS. Pain was assessed in three studies (219 patients) revealing an important advantage of stockings (P < .0001). Other subjective parameters and issues of nursing revealed an advantage of MCS as well.nnnCONCLUSIONSnLeg compression with stockings is clearly better than compression with bandages, has a positive impact on pain, and is easier to use.

Impact of obesity on venous hemodynamics of the lower limbs

BACKGROUNDnObesity 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).nnnMETHODSnVenous 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.nnnRESULTSnThe 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.nnnCONCLUSIONnLower 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.

Endovascular treatment of common femoral artery obstructions

OBJECTIVEnTo evaluate the clinical efficacy of endovascular therapy of symptomatic obstructions of the common femoral artery (CFA).nnnMETHODSnConsecutive series of patients undergoing endovascular therapy of chronic CFA obstructions between 1995 and 2009 and who were followed systematically within a prospectively maintained database. Clinical assessment was based on current guidelines including ankle-brachial index (ABI) and was performed at baseline and the day of discharge and then repeated at 3, 6, and 12 months and annually thereafter. Technical success of intervention was defined as a final residual diameter stenosis of <30%. Sustained clinical improvement was defined as a sustained upward shift of at least one category on the Rutherford classification compared with baseline without the need for repeated target lesion revascularization (TLR) or amputation in surviving patients. Limb salvage was defined as absence of a major (ie, above the ankle) amputation. Survival analysis was performed using the Kaplan-Meier method.nnnRESULTSnNinety-eight patients (38 women, mean age 72 ± 11 years) presented with 104 ischemic limbs, 20 of which (19%) were classified as having critical limb ischemia (CLI). Technical success rate was 98%. Stents were placed in eight CLI patients (40%) and in 20 claudicants (24%). Mean ABI improved from 0.28 to 0.54 (P < .001) in CLI patients and from 0.61 to 0.85 (P < .001) in claudicants. Mean follow-up was 16 months. Primary sustained clinical improvement rates at 3, 6, 12, and 24 months were 55%, 55%, 40%, and 0% in CLI patients and 81%, 75%, 68%, and 52% in claudicants, respectively. Limb salvage rates at 24 months were 94% in CLI patients and 100% in claudicants. After adjustment for confounding factors, presence of ischemic ulcers (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.49-14.85; P = .009), obstruction of the femoropopliteal arterial tract (HR, 3.9; 95% CI, 1.66-9.16; P = .002) and diabetes mellitus (HR, 2.3; 95% CI, 1.02-5.28; P = .045) were independently associated with lower rates of sustained clinical improvement.nnnCONCLUSIONSnEndovascular therapy of CFA obstruction is associated with high rates of sustained clinical success in claudicants with patent femoropopliteal outflow. Presence of ischemic skin ulcers and diabetes mellitus, however, are associated with impaired efficacy of endovascular CFA treatment.

Fixed low-dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of residual stenosis for acute ilio-femoral deep-vein thrombosis

Patients with ilio-femoral deep-vein thrombosis (DVT) are at high risk of developing the post-thrombotic syndrome (PTS). In comparison to anticoagulation therapy alone, extended venography-guided catheter-directed thrombolysis without routine stenting of venous stenosis in patients with ilio-femoral DVT is associated with an increased risk of bleeding and a moderate reduction of PTS. We performed a prospective single-centre study to investigate safety, patency and incidence of PTS in patients with acute ilio-femoral DVT treated with fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT; 20 mg rt-PA during 15 hours) followed by routing stenting of venous stenosis, defined as residual luminal narrowing >50%, absent antegrade flow, or presence of collateral flow at the site of suspected stenosis. A total of 87 patients (age 46 ± 21 years, 60% women) were included. At 15 hours, thrombolysis success ≥50% was achieved in 67 (77%) patients. Venous stenting (mean 1.9 ± 1.3 stents) was performed in 70 (80%) patients, with the common iliac vein as the most frequent stenting site (83%). One major (1%; 95% CI, 0-6%) and 6 minor bleedings (7%; 95%CI, 3-14%) occurred. Primary and secondary patency rates at 1 year were 87% (95% CI, 74-94%) and 96% (95% CI, 88-99%), respectively. At three months, 88% (95% CI, 78-94%) of patients were free from PTS according to the Villalta scale, with a similar rate at one year (94%, 95% CI, 81-99%). In conclusion, a fixed-dose USAT regimen followed by routine stenting of underlying venous stenosis in patients with ilio-femoral DVT was associated with a low bleeding rate, high patency rates, and a low incidence of PTS.

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

OBJECTIVEnTo demonstrate that abdominal pressure impacts venous flow and pressure characteristics.nnnMETHODSnVenous 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.nnnRESULTSnIntravenous 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.nnnCONCLUSIONSnExternal 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.

Impact of renal insufficiency on clinical outcomes in patients with critical limb ischemia undergoing endovascular revascularization

BACKGROUNDnPatients with renal insufficiency (RI) are frequently excluded from trials assessing various endovascular revascularization concepts in critical limb ischemia (CLI) although information on clinical outcomes is scarce.nnnMETHODSnConsecutive patients with CLI undergoing endovascular lower limb revascularization during a 4.5-year time interval at a tertiary referral center were prospectively followed over a 12-month period. Patients were grouped according to renal function defined as normal (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2); n = 108, 49.5%), moderate RI (eGFR ≥ 30-59 mL/min/1.73 m(2); n = 86, 39.5%) and severe RI, including dialysis (eGFR < 30 mL/min/1.73 m(2); n = 24, 11%). Clinical endpoints assessed were sustained clinical success, peri- and postprocedural mortality and major, above-the-ankle amputation. Sustained clinical improvement was defined as an upward shift of at least one category on the Rutherford classification compared with baseline to a level of claudication without repeated revascularization or unplanned amputation in surviving patients. Survival analysis was performed using the Kaplan-Meier method. Multivariate regression analysis was conducted in separate models for all above-mentioned clinical endpoints.nnnRESULTSnA total of 208 patients (218 limbs, mean age 77.1 ± 9.5, 131 men) underwent endovascular revascularization. Technical success rate was 95.2%, 92.5%, and 100% in patients without, moderate or severe RI. Sustained clinical success was 81.7%, 74.1%, and 51.5% in patients with normal renal function, 87.8%, 67.0%, and 63.3% with moderate, and 81.0%, 64.6%, and 50.2% with severe RI (P = .87 by log-rank) at 2, 6, and 12 months. Accordingly, major amputation rates were 9.9%, 18.2%, and 20.8% vs 9.9%, 22.6%, and 24% vs 12.5%, 16.7%, and 21.1% (P = .83, by log-rank). Mortality rates were 8.4%, 17.6%, and 26.5% in patients with normal renal function, 9.6%, 17.6%, and 30.1% with moderate and 17.5%, 26.6%, and 31.9% in patients with severe RI (P = .77, by log-rank) at corresponding intervals. Multivariate analysis revealed eGFR (hazard ratio [HR], 1.016; 95% confidence interval [CI], 1.001-1.031; P = .036), age (HR, 1.12; 95% CI, 1.061-1.189; P < .0001) and cigarette smoking (HR, 3.14; 95% CI, 1.153-8.55; P = .026) to be predictors for increased mortality within 1 year of follow-up.nnnCONCLUSIONnWhile functional lower limb outcomes were not influenced by renal function in this study, presence of RI was an independent predictor for higher mortality in CLI patients undergoing endovascular revascularization.

Integrity of venoarteriolar reflex determines level of microvascular skin flow enhancement with intermittent pneumatic compression

OBJECTIVEnTo investigate whether intermittent pneumatic compression (IPC) augments skin blood flow through transient suspension of local vasoregulation, the veno-arteriolar response (VAR), in healthy controls and in patients with peripheral arterial disease (PAD).nnnMETHODSnNineteen healthy limbs and twenty-two limbs with PAD were examined. To assess VAR, skin blood flow (SBF) was measured using laser Doppler fluxmetry in the horizontal and sitting positions and was defined as percentage change with postural alteration [(horizontal SBF--sitting SBF)/horizontal SBF x 100]. On IPC application to the foot, the calf, or both, SBF was measured with laser Doppler fluxmetry, the probe being attached to the pulp of the big toe.nnnRESULTSnBaseline VAR was higher in the controls 63.8 +/- 6.4% than in patients with PAD (31.7 +/- 13.4%, P = .0162). In both groups SBF was significantly higher with IPC than at rest (P < .0001). A higher percentage increase with IPC was demonstrated in the controls (242 +/- 85% to 788 +/- 318%) than in subjects with PAD, for each one of the three different IPC modes investigated (98 +/- 33% to 275 +/- 72%) with IPC was demonstrated. The SBF enhancement with IPC correlated with VAR for all three compression modes (r = 0.58, P = .002 for calf compression, r = 0.65, P < .0001 for foot compression alone, and r = 0.64, P = .0002 for combined foot and calf compression).nnnCONCLUSIONnThe integrity of the veno-arteriolar response correlates with the level of skin blood flow augmentation generated with intermittent pneumatic compression, indicating that this may be associated with a transient suspension of the autoregulatory vasoconstriction both in healthy controls and in patients with PAD.

Endovascular Revascularization of Below-the-Knee Arteries: Prospective Short-Term Angiographic and Clinical Follow-Up

PURPOSEnTo evaluate arterial lesion characteristics and their impact on angiographic and clinical outcomes after endovascular below-the-knee (BTK) revascularization.nnnMATERIALS AND METHODSnBetween April 2008 and June 2009, 33 patients (mean age 74.9 years) with 34 limbs and 50 arterial segments (mean lesion length 59.3 mm) undergoing endovascular BTK revascularization agreed to undergo prospective clinical and intraarterial angiographic 6-month follow-up evaluation. Clinical indication for BTK revascularization was critical limb ischemia (CLI) in 18 patients and delayed wound healing without hemodynamic evidence of CLI and intermittent claudication (IC) in 15 patients.nnnRESULTSnBinary restenosis was observed in 40% of treated segments at 6 months. Primary sustained clinical improvement was 82.4% and 55.9% at 3 months and 6 months. Lesion length was independently associated with binary restenosis (hazard ratio [HR] 1.013, 95% confidence interval [CI] 1.000-1.016, P = .05) and lower rates of primary sustained clinical improvement (HR 1.024, 95% CI 1.006-1.042, P = .008).nnnCONCLUSIONSnEndovascular BTK revascularization yields clinical and angiographic benefits both for patients with IC and for patients with CLI. Although arterial lesion length adversely affects angiographic and clinical outcomes after endovascular revascularization, limb salvage rates were substantially higher compared with the comparatively low patency rates after BTK angioplasty.

Cystic adventitial degeneration: Ectopic ganglia from adjacent joint capsules

Cystic adventitial degeneration is a rare non-atherosclerotic cause of peripheral arterial occlusive disease, mainly seen in young men without other evidence of vascular disease. Diagnosis will be established by clinical findings and by ultrasound or angiography and can be treated by excision or enucleation of the affected arterial segment or by percutaneous ultrasound-guided aspiration. However, the etiology of adventitial cysts remains unknown. We report a case of cystic adventitial degeneration showing a connection between the joint capsule and the adventitial cyst, supporting the theory that cystic adventitial degeneration may represent ectopic ganglia from adjacent joint capsules.