Frederic Baumann

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

AIMS No 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. METHODS AND RESULTS Fifty-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. CONCLUSION A 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.

Endovascular treatment of common femoral artery obstructions

OBJECTIVE To evaluate the clinical efficacy of endovascular therapy of symptomatic obstructions of the common femoral artery (CFA). METHODS Consecutive 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. RESULTS Ninety-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. CONCLUSIONS Endovascular 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.

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

BACKGROUND Patients 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. METHODS Consecutive 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. RESULTS A 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. CONCLUSION While 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.

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

PURPOSE To evaluate arterial lesion characteristics and their impact on angiographic and clinical outcomes after endovascular below-the-knee (BTK) revascularization. MATERIALS AND METHODS Between 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. RESULTS Binary 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). CONCLUSIONS Endovascular 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.

Biological variation of established and novel biomarkers for atherosclerosis: Results from a prospective, parallel-group cohort study.

BACKGROUND Biomarkers are a promising tool for the management of patients with atherosclerosis, but their variation is largely unknown. We assessed within-subject and between-subject biological variation of biomarkers in peripheral artery disease (PAD) patients and healthy controls, and defined which biomarkers have a favorable variation profile for future studies. METHODS Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65±7years) and 18 healthy control subjects (44% men, 57±7years). Blood samples were taken at baseline, and after 3-, 6-, and 12-months. We calculated within-subject (CVI) and between-subject (CVG) coefficients of variation and intra-class correlation coefficient (ICC). RESULTS Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in PAD patients than in healthy controls (P≤.05 for all). CVI and CVG of the different biomarkers varied considerably in both groups. An ICC≥0.5 (indicating moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10, MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy controls and for MMP-9, PAI-1 and sCD40L in PAD patients. CONCLUSIONS Single biomarker measurements are of limited utility due to large within-subject variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP-3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies.

Diurnal changes of lower leg volume in obese and non-obese subjects

Background/aim:Obesity is a risk factor for chronic venous disease. However, the mechanisms behind this association are poorly understood. We tested the hypothesis that obese subjects have a higher diurnal leg volume increase compared with non-obese subjects.Methods:In this prospective cohort study including obese (body mass index, BMI ⩾30 kg m−2) and non-obese (BMI ⩽25 kg m−2) subjects without venous insufficiency, lower leg volume was assessed by optoelectronic volumetry in the morning and in the evening. All subjects underwent duplex ultrasound and light reflection rheography (venous pump power and venous refill time, VRT) to investigate lower extremity venous function. A pedometer was carried between the morning and evening visit to assess the daily number of footsteps. A backward multivariable linear regression model was used to determine factors associated with diurnal lower leg volume increase.Results:Forty-two limbs in 24 obese subjects and 29 limbs in 15 non-obese subjects were analyzed. Obese subjects had larger common femoral vein diameters (17.1±2.4 vs 15.5±2.4 mm, P<0.01) and slower peak, mean and minimal velocities (25.1±10.6 vs 44.3±14.3 cm s−1; 6.8±2.4 vs 12.7±5.6 cm s−1; −0.2±6.4 vs −6.3±11.9 cm s−1; P<0.01 for all) than non-obese subjects. VRT was shorter in obese subjects (40.5±15.0 vs 51.0±12.1 s, P<0.01) and decreased significantly in the course of the day only in obese subjects (P<0.01). Obesity, male gender, CEAP (Clinical-Etiology-Anatomy-Pathophysiology) class, total time between the two visits and difference between morning and evening VRT were positively associated with higher lower leg volume increase; morning VRT and the total number of footsteps showed a negative association (P<0.04 for all).Conclusion:Obesity was found to be an independent predictor of higher diurnal leg volume increase. One potential mechanism is a progressive failure of venous valve function in the course of the day in obese subjects.

Restenosis after infrapopliteal angioplasty - clinical importance, study update and further directions.

Patients with critical limb ischemia (CLI) represent the most severe form of peripheral arterial disease (PAD) and exhibit high mortality rates. Frequently, PAD in CLI patients involves the infrapopliteal arterial segment challenging endovascular revascularization strategies. Restenosis remains the major drawback of tibial angioplasty encountered in more than two thirds of CLI patients undergoing tibial revascularization. In contrast to earlier observations, tibial patency was recently shown to be essential to attain an optimal clinical outcome in CLI patients subsequent to tibial angioplasty. The exact pathopyhsiological mechanisms of tibial restenosis remains unclear. To date, most of our knowledge on tibial restenosis and its pathophysiology is derived from coronary arteries, based on the similarity of coronary arteries to tibial artery morphology. Nervertheless, multiple antirestenosis concepts are investigated within clinical trials to reduce tibial restenosis.Purpose of the present manuscript is to provide a current update on the pathophysiology of tibial restenosis and potential antirestenosis strategies.

Erectile dysfunction – overview from a cardiovascular perspective

Erectile dysfunction (ED) is an evolving health problem with growing incidence in the ageing male population with potentially predictive value for cardiovascular and other chronic diseases. ED shares the common cardiovascular risk factors. The aetiology of ED is numerous including neurogenic, psychogenic, arteriogenic, and venogenic reasons. The origin of arteriogenic ED is frequently atherosclerosis. Patients not adequately responding to conservative measures including oral medication are often referred to further vascular diagnostics and therapy. At present, the refinements in endovascular therapy allow for minimal-invasive revascularization of erection-related arteries. The role of endovascular therapy in the complex framework of the multifactorial causes of ED requires further scientific scrutiny.

Does patency matter in patients with critical limb ischemia undergoing endovascular revascularization

Restenosis is the major drawback in patients undergoing tibial angioplasty. In contrast to earlier observations, tibial patency was shown to impact on clinical outcomes in current randomized trials and is thus attributed more importance. Accordingly, intentions to reduce tibial restenosis have been intensified. Both drug-eluting balloons (DEB) and drug-eluting stents (DES) were shown to reduce tibial restenosis when compared with its plain counterparts. However, both endovascular technologies have its limitations for tibial arterial application. While DEB technology may not address elastic recoil, a pathophysiological mechanism frequently observed in tibial arteries and a significant contributor to restenosis, currently available DES do not fully address tibial arterial lesion morphology. Purpose of the present manuscript is to outline the problem and the incidence of tibial arterial restenosis, its importance on clinical outcomes and to provide an overview on technical developments aimed at its prevention.