A randomized trial of intraarterial treatment for acute ischemic stroke.

BACKGROUND: In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS: We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS: We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

Geometrical consequences of kissing stents and the Covered Endovascular Reconstruction of the Aortic Bifurcation configuration in an in vitro model for endovascular reconstruction of aortic bifurcation.

OBJECTIVE: Kissing stents (KS) are commonly used to treat aortoiliac occlusive disease, but patency results are often lower than those of isolated stents. The Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) technique was recently introduced to reconstruct the aortic bifurcation in a more anatomical and physiological fashion. The aim of this study is to compare the geometrical consequences of various stent configurations in vitro. METHODS: Anatomic vessel phantoms of the aortoiliac bifurcation were created to accommodate stent configurations. Self-expandable nitinol KS, balloon-expandable covered KS, and two versions of the CERAB configuration were deployed, one with the iliac legs positioned inside the tapered part of the aortic cuff (1) and one with the legs deployed above this level (2). Computed tomography data were obtained to assess the geometry. The conformation ratio (D-ratio) was calculated by use of the ratio of the major and minor axes. The proximal mismatch area, mean mismatch area, and total mismatch volume were calculated. RESULTS: The highest D-ratios were observed in the nitinol KS and the CERAB configuration, implying an ideal "double-D" shape. The proximal and mean mismatch areas were four- to sixfold lower in the CERAB (1) configuration when compared with nitinol KS and CERAB (2), respectively, whereas the covered KS had the highest mismatch area. Nitinol and covered KS had the largest mismatch volume, whereas the mismatch volume was the lowest in the CERAB (1) configuration. CONCLUSIONS: Although nitinol self-expandable stents have a high stent conformation, the lowest radial mismatch was found in the CERAB (1) configuration, supporting the hypothesis that the CERAB configuration is the most anatomical and physiological reconstruction of the aortic bifurcation. Within the CERAB configuration, the two limbs are ideally positioned inside the tapering portion of the cuff, minimizing mismatch.

Endovascular aneurysm sealing for juxtarenal aneurysm using the Nellix device and chimney covered stents.

PURPOSE: To show the feasibility of the Nellix device in conjunction with a chimney technique for treating juxtarenal aneurysms in two patients who were deemed unsuitable for fenestrated endovascular aneurysm repair or open surgery. CASE REPORTS: Two men aged 83 and 81 years were referred with a juxtarenal abdominal aortic aneurysm (66 and 69 mm, respectively). Both were considered for open surgery as well as custom-made fenestrated stent-graft but deemed unsuitable for both options. They were both treated using the Nellix endoprosthesis in combination with chimney grafts to preserve the renal arteries. Technical success was achieved in both cases, with successful aneurysm exclusion and target vessel preservation (the right renal artery in the first case and both renal arteries in the second). At 6 months, duplex ultrasound and computed tomographic angiography of the first patient showed no signs of endoleak and patent renal arteries. The second patient developed a right retroperitoneal hematoma with minor extravasation near the lower pole of the right kidney for which coil embolization was necessary. The subsequent clinical sequelae led to respiratory insufficiency and ultimately death. CONCLUSION: The use of the Nellix endoprosthesis combined with chimney grafts is technically feasible. The addition of chimney grafts can increase the applicability of endovascular aneurysm sealing to treat short-neck and juxtarenal aneurysms. Further studies are needed to confirm these findings and establish longer term outcome.

Use of flow-diverting stents to treat para-anastomotic iliac artery aneurysms after previous open aortic prosthetic reconstruction.

PURPOSE: To present a series of para-anastomotic iliac artery aneurysms treated with flow-diverting stents. CASE REPORTS: Three patients (2 men, 1 woman; ages 70, 73, and 78 years) with previous open aortoiliac reconstructions received a 12-mm-diameter Cardiatis Multilayer Stent to treat 4 para-anastomotic iliac artery aneurysms in an attempt to preserve their ipsilateral hypogastric arteries. After 1-year follow-up, all aneurysms were successfully excluded, with complete sac thrombosis in three and partial thrombosis in one. The diameter of the aneurysm was reduced in all by a median 6 mm. At 1 year, patency of the hypogastric artery was maintained in only the patient with partial sac thrombosis. No patient developed buttock claudication. CONCLUSION: The use of flow-diverting stents for para-anastomotic iliac artery aneurysms resulted in reduction of iliac aneurysm diameter. However, intended patency of the ipsilateral hypogastric artery was not always observed. The feasibility of the technique has therefore not been shown for this specific indication.

Outcome of thrombolysis and thrombectomy for thrombosed endografts inserted in the superficial femoral artery for occlusive disease.

PURPOSE: To evaluate the efficacy and outcome of thrombolysis and thrombectomy for thrombosed polytetrafluoroethylene stent-grafts inserted in the superficial femoral artery (SFA) for occlusive disease. METHODS: A retrospective review was conducted of 79 consecutive patients with a thrombosed SFA endograft between November 2001 and December 2011. Of these, 46 (58%) were treated with thrombolysis (n=40, 87%) or thrombectomy (n=6, 13%) and form the study group (33 men; median age 66.8 years, range 30-80). Median time from stent-graft insertion to thrombosis was 3 months (range 0-53). RESULTS: Thrombolysis was successful in 38 (95%) patients over a mean 24 hours (range 3-48); one patient had failed lysis and another died during lytic treatment. Thrombectomy was successful in all 6 patients. Thrombosis without a causal lesion was significantly more common in occlusions that presented <30 days after insertion (p=0.01). Over a median follow-up of 14 months (range 1-69), reinterventions were performed for restenosis in 12 patients and reocclusion in 14 patients, all within 18 months after thrombolytic treatment. More than a third of patients (16/45) had definitive failures (2/6 from the thrombectomy group); 4 were treated conservatively (no/minor symptoms) and 12 had bypass grafts. Three (7%) patients eventually required a major amputation. The primary, assisted primary, and secondary patency rates of thrombolysis at 6 months were 56%, 56%, and 68%, respectively. Secondary patency for the entire cohort was 58% at 1 year. CONCLUSION: Thrombolysis and thrombectomy of thrombosed endografts in the SFA is effective and safe. Patency rates after treatment are moderate, but prolonged secondary patency can be achieved.

Results of heparin-bonded ePTFE-covered stents for chronic occlusive superficial femoral artery disease.

OBJECTIVE: The purpose of this study was to assess the 1-year patency rates of heparin-bonded covered stents in the treatment of chronic occlusive disease of the superficial femoral artery (SFA). METHODS: All patients treated with a heparin-bonded endograft between April 2009 and October 2010 for chronic occlusive disease of the SFA were prospectively gathered in a database and retrospectively analyzed. Primary, primary-assisted, and secondary patency rates, assessed by ultrasound scanning, were analyzed at 1-year, as were the complication rates and mortality. RESULTS: A total of 56 limbs were treated with a heparin-bonded covered stent in 53 patients for chronic ischemia Rutherford category 3 (n = 36), 4 (n = 5), 5 (n = 11), and 6 (n = 1). Lesions were classified as TransAtlantic Inter-Society Consensus (TASC)-2-B (n = 9), C (n = 14), and D (n = 33), and the mean treated lesion length was 18.5 ± 7.7 cm. Postoperative complications occurred in 7.5%, including hematoma (n = 1), edema (n = 1), pneumonia (n = 1), and urinary retention (n = 1), and the 30-day mortality rate was 0%. The mean follow-up was 413 ± 208 days. At 1 year, the primary patency was 76%, the primary-assisted patency 82%, and the secondary patency 89%. The limb salvage rate was 100%. CONCLUSIONS: Heparin-bonded covered stents seem to provide a valid alternative to surgical treatment of long occlusive lesions in the SFA. Randomized trials and long-term data are required before considering the technique as a new standard of care.

Primary balloon expandable polytetrafluoroethylene-covered stenting of focal infrarenal aortic occlusive disease.

BACKGROUND: Focal infrarenal aortic occlusive disease requiring treatment is an uncommon condition. Short lesions may be treated endovascularly, while long lesions are traditionally treated by surgery. Advances in endovascular devices, including development of covered stents, may expand endovascular options. This study evaluates the feasibility, safety, and midterm results of primary polytetrafluoroethylene (PTFE)-covered stenting of isolated atherosclerotic lesions of the infrarenal aorta. MATERIAL AND METHODS: Between November 2008 and March 2011, 12 patients, aged 59 (42 to 78) years, were treated with a balloon-expandable PTFE-covered stent for a focal infrarenal aortic stenosis (n = 11) or occlusion (n = 1). Indications included disabling claudication (n = 9), rest pain (n = 1), or minor tissue loss (n = 2) Follow-up consisted of clinical examination, ankle-brachial indexes, plain abdominal radiography and duplex ultrasonography. RESULTS: Eleven procedures were performed percutaneously and one in combination with an endarterectomy of the right common femoral artery. Technical success was 100%, and clinical improvement was achieved in all but one patient, who needed additional femoropopliteal bypass surgery. The median follow-up was 18 months (range 2-30 months). During follow-up, all patients remained asymptomatic and ankle-brachial indexes had normalized. Duplex ultrasonography showed no re-stenosis, and there were no stent fractures on abdominal radiographs. CONCLUSIONS: The primary use of PTFE-covered stents is a feasible, effective, and safe treatment for focal atherosclerotic lesions in the infrarenal aorta. Comparative studies with traditional treatment modalities, however, are indicated before considering the use of covered stents as standard treatment.

Endovascular repair of a ruptured type II renal artery aneurysm using an endograft.

BACKGROUND: The purpose of this study was to describe a case of an endovascular exclusion of a ruptured type II renal artery aneurysm in a hemodynamically unstable patient using an endograft. METHODS AND RESULTS: A 73-year-old woman, with an extensive medical history, presented with a sudden onset of abdominal pain and hypovolemic shock. A computed tomography scan showed a massive right-sided retroperitoneal hematoma and a type II aneurysm of the right renal artery just proximal to the bifurcation. Angiography demonstrated active contrast extravasation from the aneurysm. The aneurysm was excluded using a 5-cm long, 6-mm wide endograft. After a 6-month interval, duplex ultrasonography showed a patent endograft and normal perfusion of the renal parenchyma in the lower and middle pole, with a glomerular filtration rate of 75 mL/min. CONCLUSION: Endovascular exclusion using an endograft may provide a safe and rapid alternative to surgery to treat ruptured renal artery aneurysms in a selected group of patients.

Endovascular versus surgical revascularization in proximal subclavian artery obstruction.

BACKGROUND: The aim of this paper was to compare the outcomes of endovascular versus surgical treatment in patients with symptomatic proximal subclavian artery obstruction through a retrospective clinical study. Treatment of symptomatic subclavian artery obstruction can be performed with percutaneous transluminal angioplasty or open surgical reconstruction. Comparative studies are scarce. METHODS: Technical success, patency and complication rates of 47 endovascular reconstructions in 46 patients were retrospectively compared with those of 19 open surgical reconstructions in 17 patients performed between 1996 and 2012. An additional series of 51 surgical reconstructions performed in the same institution between 1976 and 1993 served as a reference. RESULTS: The technical success rate was 79% for endovascular and 100% for open surgical reconstructions (P<0.05). Primary patency was 72% and 89% at 1 year or 54% and 55% at 5 years for the endovascular and open surgical groups, respectively (log rank 0.210, P=0.65). Assisted primary patency was 77% and 100% at 1 year or 67% and 67% at 5 years, respectively (log rank 0.528, P=0.47). There was no mortality and major complications were infrequent, occurring equally in both groups (P=0.22). CONCLUSIONS: Although with its less invasive character endovascular treatment has gained preference over surgical treatment of proximal subclavian obstruction in many cases, extrathoracic surgical reconstruction can be performed with a higher technical success rate, similar patency and a comparable number of complications.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial.

IMPORTANCE: Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE: To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS: The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES: Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS: Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE: For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1804.

The contribution of factor V Leiden and prothrombin G20210A mutation to the risk of central venous catheter-related thrombosis.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the incidence of central venous catheter (CVC)-related thrombosis and the contribution of two common inherited coagulation disorders (factor V Leiden, prothrombin G20210A mutation) to this complication in a large hospital population. DESIGN AND METHODS: In a prospective setting, patients were assessed daily for signs and symptoms suggestive of thrombosis. Routine Doppler-ultrasound was performed weekly in all patients until CVC removal. Doppler-ultrasound examinations were stored on videotape and assessed by two blinded observers. In the case of clinically suspected thrombosis the physicians followed routine diagnostic and therapeutic procedures. The presence of factor V Leiden and prothrombin G20210A mutation and other potential risk factors were assessed in all patients. RESULTS: In 252 consecutive patients the cumulative incidence of-CVC related thrombosis was 30% (clinically manifested thrombosis: 7%). The relative risk of factor V Leiden or prothrombin G20210A mutation for thrombosis was 2.7 (CI95% 1.9 to 3.8). In addition, a personal history of venous thrombosis was associated with CVC-related thrombosis, whereas the severity of thrombosis was affected by the absence of anticoagulants and the presence of cancer. INTERPRETATION AND CONCLUSIONS: Thrombosis is frequently observed after central venous catheterization. Common inherited abnormalities in blood coagulation contribute substantially to CVC-related thrombosis. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in vulnerable patients, a priori determination of common inherited and acquired risk factors may form a basis to guide these treatment decisions.

Endovascular repair of a Streptococcus pneumonia-induced aortitis complicated by an iliacocaval fistula.

PURPOSE: To describe the successful endovascular treatment and follow-up of a patient with a Streptococcus pneumonia-induced right iliacocaval fistula. CASE REPORT: A 82-year-old man was diagnosed with a right iliacocaval fistula, as a result of Streptococcus pneumoniae infection of the distal aorta and proximal right common iliac artery. After antibiotic treatment, he was initially unsuccessfully treated with balloon expandable covered stents. Then, the fistula was excluded by an aortamonoiliac endograft to the left common iliac artery, and occluders in the distal and proximal right common iliac artery followed by a femoral-femoral crossover bypass. Postoperatively patient was treated with prolonged antibiotics. After a follow-up of 20 months, there are no signs of active infection, endoleak, or fistula, both clinically and on 2-deoxy-2-[F18]fluoro-D-glucose positron emission tomography/computed tomography. CONCLUSION: In selected patients, complicated infectious disease of the aorto-iliac tract may be treated successfully with an endograft and prolonged antibiotics.

Initial results of catheter-directed ultrasound-accelerated thrombolysis for thromboembolic obstructions of the aortofemoral arteries: a feasibility study.

PURPOSE: This article reports the 30-day technical and clinical outcome of ultrasound (US)-accelerated thrombolysis in patients with aortofemoral arterial thromboembolic obstructions. METHODS: A prospective cohort study was conducted from December 2008 to December 2009 of patients who were treated with US-accelerated thrombolysis for thromboembolic obstructions of aortofemoral arteries or bypasses. Urokinase was infused in a dosage of 100,000 IU per hour. Twice daily, a control angiography was performed. Thirty-day follow-up consisted of duplex scanning, combined with magnetic resonance angiography. RESULTS: The study included 21 consecutive patients (20 men; median age, 66 (range, 52-80) years) with 24% artery versus 76% bypass occlusions. Median duration of symptoms was 11 (range, 7-140) days. Median occlusion length was 32 (range, 6-80) cm. In 20 patients (95%), an US-accelerated thrombolysis catheter could be successfully placed. In one patient, placement of an US-accelerated thrombolysis catheter was technically not feasible, and therefore a standard catheter was placed. Median thrombolysis time was 26.5 (range, 8.5-72) hours. Complete thrombolysis (>95% lysis of thrombus) was achieved in 20 patients; in 9 patients within 24 hours. Median ankle-brachial index (ABI) increased from 0.28 (range, 0-0.85) to 0.91 (range, 0.58-1.35). One patient had a thromboembolic complication and needed surgical intervention. No hemorrhagic complications, and no deaths occurred. At 30-day follow-up, 17 of 21 patients (81%) had a patent artery or bypass. CONCLUSIONS: This feasibility study showed a high technical success rate of US-accelerated thrombolysis for aortofemoral arterial obstructions. US-accelerated thrombolysis led to complete lysis within 24 hours in almost half of patients, with a low 30-day major complication rate.

Dutch randomized trial comparing standard catheter-directed thrombolysis versus ultrasound-accelerated thrombolysis for thromboembolic infrainguinal disease (DUET): design and rationale.

BACKGROUND: The use of thrombolytic therapy in the treatment of thrombosed infrainguinal native arteries and bypass grafts has increased over the years. Main limitation of this treatment modality, however, is the occurrence of bleeding complications. Low intensity ultrasound (US) has been shown to accelerate enzymatic thrombolysis, thereby reducing therapy time. So far, no randomized trials have investigated the application of US-accelerated thrombolysis in the treatment of thrombosed infra-inguinal native arteries or bypass grafts. The DUET study (Dutch randomized trial comparing standard catheter-directed thrombolysis versus Ultrasound-accElerated Thrombolysis for thrombo-embolic infrainguinal disease) is designed to assess whether US-accelerated thrombolysis will reduce therapy time significantly compared with standard catheter-directed thrombolysis. METHODS/DESIGN: Sixty adult patients with recently (between 1 and 7 weeks) thrombosed infrainguinal native arteries or bypass grafts with acute limb ischemia class I or IIa, according to the Rutherford classification for acute ischemia, will be randomly allocated to either standard thrombolysis (group A) or US-accelerated thrombolysis (group B). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is the duration of catheter-directed thrombolysis needed for uninterrupted flow in the thrombosed infrainguinal native artery or bypass graft, with outflow through at least 1 crural artery. DISCUSSION: The DUET study is a randomized controlled trial that will provide evidence of whether US-accelerated thrombolysis will significantly reduce therapy time in patients with recently thrombosed infrainguinal native arteries or bypass grafts, without an increase in complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72676102.

Delayed pseudoaneurysm after renal artery angioplasty.

PURPOSE: To report delayed pseudoaneurysm formation after percutaneous renal artery angioplasty. CASE REPORTS: A 56-year-old woman succumbed to complications of a ruptured right juxtarenal aortic pseudoaneurysm 2 years after right renal artery stenting for renal impairment. The juxtarenal aorta had been normal on aortography at the time of angioplasty. She gave a history of right-sided back pain that started within 8 months of the angioplasty. A 21-year-old woman with left renal artery stenosis due to fibromuscular dysplasia was treated with balloon angioplasty, after which there was evidence of active extravasation. The completion angiogram, after a period of observation, documented cessation of the leak. Follow-up angiography because of persisting hypertension disclosed a large, asymptomatic, intrarenal pseudoaneurysm that was repaired with bench surgery and autotransplantation. CONCLUSIONS: We advise that patients with symptoms referable to the site of renal artery intervention and those who have had complicated interventions should have follow-up imaging to exclude pseudoaneurysm formation.

Prospective study of renal insufficiency after bone marrow transplantation.

Since more and more children survive allogeneic bone marrow transplantation (BMT), knowledge of acute and late complications becomes increasingly important. Besides the major complications [(opportunistic) infections, veno-occlusive disease, graft versus host disease, and recurrence of primary disease], acute and chronic renal insufficiency are significant post-transplant complications that may contribute to transplant-related mortality. To elucidate risk factors for acute and chronic renal insufficiency post BMT, we performed a prospective study of all 66 children who received a BMT in a 2-year period at our institution; 21% had acute renal insufficiency post BMT. Risk factors for acute renal insufficiency were veno-occlusive disease, high cyclosporin serum levels, and foscarnet therapy. Of surviving patients, 11% developed chronic renal insufficiency 1 year post BMT. Acute renal insufficiency was the sole predictor of chronic renal insufficiency. In contrast to studies in adults, we did not find total body irradiation to be a risk factor for chronic renal insufficiency. Future long-term studies are needed to assess incidence and morbidity of chronic renal insufficiency in children following allogeneic BMT.

Central venous catheter related thrombosis in haematology patients and prediction of risk by screening with Doppler-ultrasound.

Patients with a central venous catheter (CVC) who receive intensive chemotherapy or a stem cell transplantation for haematological disease are at risk for developing CVC-related thrombosis. To study the incidence of thrombosis, 105 consecutive patients underwent serial Doppler-ultrasound and we evaluated whether clinically manifest thrombosis could be predicted by screening with Doppler-ultrasound. Patients with subclavian or jugular inserted CVCs were clinically assessed each day for signs and symptoms of thrombosis. Additional Doppler-ultrasound screens were performed weekly by an independent physician in all patients until CVC removal. Doppler-ultrasound recordings were assessed by two blinded observers. In cases of clinically suspected thrombosis, the attending physicians followed routine diagnostic and therapeutic procedures. The overall cumulative incidence of CVC-related thrombosis was 28.6% (30 of 105 patients). Of the 30 patients with thrombosis, 26 had subclinical thrombosis by Doppler-ultrasound, nine of whom developed clinically manifest thrombosis later. Four patients had clinically manifest thrombosis without prior abnormal Doppler-ultrasound. In cases of subclinical thrombosis the risk of developing symptomatic disease increased sevenfold (34.6% vs. 5.1%). Doppler-ultrasound screening may be useful to identify those patients that are at high and low risk for clinically manifest CVC-related thrombosis.