Gunnar Sandbæk

Catheter‐directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short‐term patency

Summary.  Background: Approximately one in four patients with acute proximal deep vein thrombosis (DVT) given anticoagulation and compression therapy develop post‐thrombotic syndrome (PTS). Accelerated removal of thrombus by thrombolytic agents may increase patency and prevent PTS. Objectives: To assess short‐term efficacy of additional catheter‐directed thrombolysis (CDT) compared with standard treatment alone. Patients and methods: Open, multicenter, randomized, controlled trial. Patients (18–75 years) with iliofemoral DVT and symptoms < 21 days were randomized to receive additional CDT or standard treatment alone. After 6 months, iliofemoral patency was investigated using duplex ultrasound and air‐plethysmography assessed by an investigator blinded to previous treatment. Results: One hundred and three patients (64 men, mean age 52 years) were allocated additional CDT (n = 50) or standard treatment alone (n = 53). After CDT, grade III (complete) lysis was achieved in 24 and grade II (50%–90%) lysis in 20 patients. One patient suffered major bleeding and two had clinically relevant bleeding related to the CDT procedure. After 6 months, iliofemoral patency was found in 32 (64.0%) in the CDT group vs. 19 (35.8%) controls, corresponding to an absolute risk reduction (RR) of 28.2% (95% CI: 9.7%–46.7%; P = 0.004). Venous obstruction was found in 10 (20.0%) in the CDT group vs. 26 (49.1%) controls; absolute RR 29.1% (95% CI: 20.0%–38.0%; P = 0.004). Femoral venous insufficiency did not differ between the two groups. Conclusions: After 6 months, additional CDT increased iliofemoral patency from 36% to 64%. The ongoing long‐term follow‐up of this study will document whether patency is related to improved functional outcome.

Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial

BACKGROUND Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT) and is associated with reduced quality of life and a substantial cost burden. In the 2-year results of the CaVenT study, additional catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life. In this study we report results at the 5-year follow-up, aiming to assess whether findings for post-thrombotic syndrome and quality of life have persisted. METHODS Between Jan 3, 2006, and Dec 22, 2009, we recruited patients aged 18-75 years with a first-time high proximal leg DVT from 20 hospitals in the Norwegian southeastern health region. With sealed envelopes, participants were randomly assigned (1:1) to standard treatment with compression stockings and anticoagulants (control group) or to standard treatment plus catheter-directed thrombolysis with alteplase within 21 days from symptom onset. Pre-specified outcomes in this analysis were post-thrombotic syndrome at 5 years as assessed with the Villalta score and scores for quality of life at 5 years with EQ-5D and the disease-specific VEINES-QOL/Sym. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00251771. FINDINGS At 5 year follow-up (last date Oct 14, 2014), data were available for 176 patients (84% of the 209 patients originally randomised)--87 originally assigned to catheter-directed thrombolysis and 89 originally assigned to the control group. 37 patients (43%; 95% CI 33-53) allocated to catheter-directed thrombolysis developed post-thrombotic syndrome, compared with 63 (71%; 95% CI 61-79) allocated to the control group (p<0·0001), corresponding to an absolute risk reduction of 28% (95% CI 14-42) and a number needed to treat of 4 (95% CI 2-7). Four (5%) patients assigned to catheter-directed thrombolysis and one (1%) to standard treatment had severe post-thrombotic syndrome (Villalta score ≥ 15 or presence of an ulcer). Quality-of-life scores with either assessment scale did not differ between the treatment groups. INTERPRETATION Additional catheter-directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter-directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life. The optimal endovascular thrombolytic approach needs further investigation. FUNDING Southeastern Norway Regional Health Authority, the Research Council of Norway, University of Oslo, Oslo University Hospital.

Markers of vascular inflammation are associated with the extent of atherosclerosis assessed as angiographic score and treadmill walking distances in patients with peripheral arterial occlusive disease

The importance of inflammation in atherosclerosis is well established in cardiovascular disease. However, limited data exist on the relationship between vascular inflammation and the severity of peripheral arterial occlusive disease (PAD). We investigated the relationship between biochemical markers of vascular inflammation and the diagnostic measures of PAD: ankle-brachial pressure index (ABI), maximum treadmill walking distance and angiographic score. In 127 patients (mean age 66 years; 64% males) with angiographically verified PAD, fasting blood samples were drawn for determination of selected soluble cell adhesion molecules, cytokines and chemokines. Tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and CD40 ligand (CD40L) were all significantly correlated with the angiographic score (p < 0.05 for all). After adjustment for relevant co-variates, MCP-1 and CD40L remained statistically significant (p < 0.01 for both). IL-6 was, independent of other risk factors, inversely correlated with the maximum treadmill walking distance (p < 0.01). Our cross-sectional study in PAD patients showed that the vascular inflammatory markers MCP-1, CD40L and IL-6 were significantly associated with the extent of atherosclerosis, assessed by angiographic score and maximum treadmill walking distance. These findings indicate that vascular inflammation is implicated in PAD, which might be of importance in future diagnosis and treatment of the disease.

Stenting for Chronic Post-thrombotic Vena Cava and Iliofemoral Venous Occlusions: Mid-term Patency and Clinical Outcome

OBJECTIVES The aim of this study was to determine the mid-term patency and the clinical outcome after stenting of chronic occluded caval and iliofemoral venous segments. DESIGN Observational study. MATERIAL/METHODS During the period 2000 and 2009, 2400 patients with chronic venous insufficiency (CVI) were evaluated, and 34 with chronic venous occlusions after deep venous thrombosis (DVT) were selected for endovascular treatment. The median age was 41 (range 15-63) years, and 19 were female. The following investigations were undertaken: colour duplex ultrasound (CDU), ascending venography (AV), venous occlusion plethysmography (VOP), venous pressure gradient (VPG) and CT venography or trans-femoral/popliteal venography. The major symptoms were venous claudication, oedema, pain and ulcer. All patients were treated by stenting occluded segments. Self-expanding stents were deployed in 22 iliofemoral, nine iliac and one caval-iliac-femoral. Twenty-one procedures required stenting across the inguinal ligament. RESULTS Primary recanalisation was accomplished in 32/34 (94%). The median follow-up was 33 months (1-96) with clinical examination, CDU and VOP. Two-year primary patency was 14/21 (67%), primary-assisted patency 16/21(76%), and secondary patency was 19/21 (90%). Venous claudication and oedema resolved in those successfully recanalised. Four of the seven ulcers healed. CONCLUSION Stenting to treat venous claudication, oedema and recurrent venous ulcer caused by post-thrombotic chronic venous occlusions has positive clinical outcome and good mid-term patency.

Noninvasive coronary angiography with 64-channel multidetector computed tomography in patients with acute coronary syndrome:

Background: Advances in computer tomography (CT) imaging technology in recent years have facilitated the possibility of noninvasive coronary angiography. Purpose: To compare the diagnostic accuracy of 64-channel multidetector computed tomography (MDCT) with conventional invasive coronary angiography (ICA) for the detection of significant coronary stenosis in patients with acute coronary syndrome (ACS). Material and Methods: MDCT was performed in 60 patients classified with non-ST-elevation infarction (NSTEMI) or unstable angina and scheduled for ICA within 3 days. The diagnostic accuracy of MDCT was evaluated using quantitative coronary angiography (QCA) as the gold standard. Results: 48 out of 60 patients had interpretable scans by both MDCT and ICA. On a segment-based analysis, 488 out of 665 segments with a diameter of ≥1.5 mm, as defined by QCA, were interpretable by MDCT. Sensitivity was 78%, specificity 87%, positive predictive value 47%, and negative predictive value 97% in detecting and excluding significant coronary stenosis, as defined with MDCT. On a per patient-based analysis, sensitivity was 89%, specificity 50%, positive predictive value 84%, and negative predictive value 60%. Conclusion: Limited diagnostic accuracy restricts the usefulness of coronary MDCT in patient groups with a high pretest probability of disease, such as in acute coronary syndrome.

Beneficial effects of 1-year optimal medical treatment with and without additional PTA on inflammatory markers of atherosclerosis in patients with PAD. Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT) study

The influence of optimal medical treatment (OMT) with or without additional percutaneous transluminal angioplasty (PTA) on vascular inflammation in peripheral arterial occlusive disease (PAD) patients was investigated. Patients with intermittent claudication (IC) and angiographically verified PAD were randomized to OMT (n = 28) or OMT + PTA (n = 28) and followed for 12 months. Ankle—brachial index (ABI), treadmill walking distances (WD), visual analogue scale (VAS), and blood sampling for the determination of selected soluble biomarkers were undertaken at baseline and after 3 and 12 months. After both 3 and 12 months, ABI, WD and VAS were highly significantly improved in favour of OMT + PTA (p < 0.05 for all). Significant improvements were recorded in both groups in serum lipids (p < 0.01 for all), except for triglycerides, and in the inflammatory markers P-selectin, interleukin-6, interleukin-10, monocyte chemoattractant protein-1 and fibrinogen (p < 0.05 for all). There were, however, no differences in the changes from baseline between the groups in any variable. Intervention with OMT alone or in combination with PTA did not differ with regard to the effects on serum lipids and markers of inflammation in our population of PAD patients. The combined treatment was, however, better for the treadmill walking distance.

Prothrombotic activity is associated with the anatomical as well as the functional severity of peripheral arterial occlusive disease

The importance of prothrombotic activity in cardiovascular disease has been well established. However, limited data exist on the relationship between prothrombotic activity and the severity of peripheral arterial occlusive disease (PAD). The objective of the present study was to investigate the relationship between markers of haemostasis and the diagnostic measures of PAD: ankle-brachial-index (ABI), maximum treadmill walking distance and angiographic score. In a cross-sectional study of 127 patients (mean age 66 years; 64% males) with angiographically verified PAD, fasting blood samples were drawn, and citrated plasma was obtained for determination of selected haemostatic variables: von Willebrand factor (vWF), thrombomodulin (sTM), thrombin-antithrombin complex (TAT), soluble tissue factor (sTF), tPA antigen (tPAag) and D-dimer were all significantly correlated with the angiographic score (p < 0.05 for all). D-dimer, tPAag and fibrinogen were inversely correlated with the maximum treadmill walking distance, (p < 0.0001, p < 0.04 and p < 0.05, respectively), whereas fibrinogen was the only variable correlating to ABI (r = -0.223, p < 0.05). After adjustment for relevant covariates, D-dimer and TAT remained statistically significantly associated with the angiographic score (p < 0.001), and fibrinogen was, independent of other risk factors, inversely related with both the maximum treadmill walking distance and the ABI (p < 0.01 for both). This rather large study in patients with PAD showed that plasma levels of D-dimer, TAT and fibrinogen significantly predicted the extent of atherosclerosis, evaluated by angiographic score, maximum treadmill walking distance and ABI, respectively. These findings demonstrate a prothrombotic state in PAD patients, which might be of importance in future diagnosis and treatment of the disease.

Twelve-Months Follow-up of Supervised Exercise after Percutaneous Transluminal Angioplasty for Intermittent Claudication: A Randomised Clinical Trial

The aim of this study was to explore the effects during 12 months follow-up of 12 weeks of supervised exercise therapy (SET) after percutaneous transluminal angioplasty (PTA) compared to PTA alone on physical function, limb hemodynamics and health-related quality of life (HRQoL) in patients with intermittent claudication. Fifty patients were randomised to an intervention or a control group. Both groups received usual post-operative care and follow-up measurements at three, six and 12 months after PTA. The intervention group performed 12 weeks of SET after PTA. The control group did not receive any additional follow-up regarding exercise. During the 12 months’ follow-up, the members of the intervention group had significantly better walking distance than the control group. The intervention group had a significantly higher HRQoL score in the physical component score of the SF-36, and the domains of physical function, bodily pain and vitality. For limb hemodynamics, there was a non-significant trend towards better results in the intervention group compared to the control group. Conclusion: SET after PTA yielded statistically significantly better results for walking distance and HRQoL in the intervention group than the control group during the 12 months of follow-up.

The smoothness of unconstrained head movements is velocity-dependent

Non-smooth, irregular movements reported in persons with neck pain have been suggested to signify motor impairment. However, irregular movements are additionally observed during slow movements in healthy participants. We therefore examined whether the smoothness of head movements is related to the movement speed in 26 healthy participants. Six unconstrained small and large amplitude head movements were completed in the sagittal plane at three different self-chosen speeds. Kinematic variables were calculated from position data and overall smoothness of the movement was assessed by the normalized jerk cost (NJC). Relationship between NJC and average movement angular velocity was analyzed using a mixed factor model. Movement duration, angular velocity, NJC and number of submovements differed significantly between speed conditions for all movement directions and amplitudes (all p<.05). We found a strong relationship between the average angular velocity and NJC across all movement directions and amplitudes (all p<.0001). Large amplitude movements showed higher NJC for a given movement velocity than small amplitude movements (p<.001). We have shown that the smoothness of head movements is strongly related to the movement velocity, thus fast movements are smooth while slow movements are jerky. In addition, movements of larger amplitude are less smooth than movements of smaller amplitude.

Review of postoperative CT and ultrasound for endovascular aneurysm repair using Talent stent graft: can we simplify the surveillance protocol and reduce the number of CT scans?

Background Simplifying a postoperative surveillance protocol for endovascular aneurysm repair (EVAR) requires quality control comparing computerized tomography (CT) and ultrasound (US) results of abdominal aortic aneurysm (AAA) diameter measurements and endoleaks. Purpose To test if US is comparable to CT, then assess a simplified follow-up with our conventional surveillance to assess patient safety. Material and Methods During 2001-2006, data on 56 patients treated with Talent stent graft were prospectively registered. Median follow-up was 41.5 months (range, 2-94 months), with CT, US, and plain film abdomen X-rays (PFA) at 1, 6, and 12 months, then yearly. Bland-Altman plot was used to assess the agreement between CT and US measuring the AAA diameters and mixed model by the time effect to assess the difference in diameter over time. Sensitivity and specificity for detection of endoleaks by US, with CT as ‘gold standard’ were calculated. A simplified surveillance protocol with US/PFA at 6 and 8 weeks, CT/US/PFA at 1 year, and yearly US/PFA thereafter, was evaluated. CT was carried out when poor visibility, endoleak detected, AAA diameter increase (≥5 mm) on US or migration (≥10 mm) on PFA. This regime was compared with our conventional follow-up protocol. Results Diameter measurements on US appear comparable to CT with 91% specificity and 85% sensitivity for endoleaks detected by US. Using the simplified surveillance protocol no endoleaks, migrations, or endotension requiring treatment were overlooked. The simplified protocol generated 53 selective CT scans, avoiding approximately 144 CT scans. If further simplified by omitting the 1-year CT scan, one type II endoleak would be missed with a 1-year delay, eliminating a further 45 CT scans. Conclusion US appears comparable to CT in the follow-up of Talent stent grafts in our institution. The proposed simplified surveillance protocol seems safe and can lead to a significant reduction in the number of CT scans.