Towards improvement in deep vein thrombosis : Studies on diagnostic MRI, thrombolytic therapy, and quality of life
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AbstractBackground: Standard treatment for deep vein thrombosis includes anticoagulation and compression therapy. Accelerated lysis of venous thrombus by additional catheter-directed thrombolysis is suggested to reduce the development of postthrombotic syndrome. Large scale randomized controlled trials with long-term follow-up are needed to evaluate additional thrombolysis compared with standard treatment alone. Traditionally clinical trials on deep vein thrombosis have not employed functional outcomes with assessment of postthrombotic syndrome and quality of life, and this should be included. Routine diagnostic imaging with ultrasound for detection of acute deep vein thrombosis is not always feasible.
Aims: The overall objective was to evaluate and improve diagnostic imaging and therapy of deep vein thrombosis of the lower limb with focus on catheter-directed thrombolysis and MRI. The first aim was to design and implement a well designed trial for the evaluation of additional catheter-directed thrombolysis. The second aim was translation and psychometric evaluation with assessment of data quality, reliability and validity, of a disease-specific questionnaire for patient reported quality of life following venous thrombosis of the lower limb. Final aim was to compare balanced MRI with contrast-enhanced MRI in visualisation of the deep veins and detection of acute deep vein thrombosis with ultrasound as reference method.
Materials and methods: In the CaVenT Study a total of 200 patients with acute iliofemoral deep vein thrombosis will be recruited to detect a clinically relevant reduction in postthrombotic syndrome from 25 % to 10 % after 2 years. The patients are randomized to receive additional thrombolysis or standard treatment alone. The first 118 recruited patients were included in the analyses on short-term patency. Noninvasive assessment of veins, clinical assessment of postthrombotic syndrome, and patient-reported outcome on quality of life were performed after 6 and 24 months. The quality of life validation study was performed on a subset of 74 patients in the CaVenT Study using a novel Norwegian translation of the VEINES-QOL/Sym questionnaire. Balanced and contrast enhanced MRI were performed in 15 healthy volunteers and 6 patients with proximal deep vein thrombosis verified with ultrasound.
Results: A psychometric evaluation of the Norwegian version of the VEINES-QOL/Sym questionnaire indicated satisfactory data quality, item-total correlations, internal consistency, test-retest reliability, and construct validity. Additional catheter-directed thrombolysis resulted in effective lysis in the great majority of patients. After 6 months venous patency was improved (64.0% vs. 35.8%) and venous obstruction was reduced (20.0% vs. 49.1%) when comparing additional thrombolysis with standard treatment alone. Venous incompetence was detected in the majority of patients, and did not differ between the two groups. Balanced and contrast-enhanced MRI techniques were comparable in visualizing the deep veins of the lower limb. Diagnostic properties and inter-observer reliability of both MRI sequences were good for proximal and poor for distal deep vein thrombosis.
Conclusions: The CaVenT study is a considerable contribution towards a more evidence-based practice in the treatment of deep vein thrombosis, and future long-term results may lead to a modification of clinical guidelines. The psychometric properties of the Norwegian version of the VEINES-QOL/Sym questionnaire support its use in the evaluation of patient outcomes and burden of illness in clinical studies on deep vein thrombosis. Additional catheter-directed thrombolysis improved short-term venous patency compared to anticoagulation and compression therapy only. Both balanced and contrast-enhanced MRI may be used for the detection of proximal deep vein thrombosis in patients where ultrasound is not feasible.
List of papers
Paper I Enden T, Sandvik L, Kløw NE, Hafsahl G, Holme PA, Holmen PO, Ghanima W, Njaastad AM, Sandbæk G, Slagsvold CE, and Sandset PM. Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis - the CaVenT Study: Rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771). American Heart Journal 2007;154:808-14. doi:10.1016/j.ahj.2007.07.010
Paper II Enden T, Garratt AM, Kløw NE, and Sandset PM. Assessing burden of illness following acute deep vein thrombosis: data quality, reliability and validity of the Norwegian version of VEINES-QOL/Sym, a disease-specific questionnaire. Scandinavian Journal of Caring Sciences 2009;23:369-74 doi:10.1111/j.1471-6712.2008.00618.x
Paper III Enden T, Sandvik L, Kløw NE, Hafsahl G, Holme PA, Holmen PO, Ghanima W, Njaastad AM, Sandbæk G, Slagsvold CE, and Sandset PM. Catheter-directed thrombolysis versus anticoagulant therapy alone in deep vein thrombosis: Results of an open randomized, controlled trial reporting on short term patency. Journal of Thrombosis and Haemostasis 2009;7:1268-75. doi:10.1111/j.1538-7836.2009.03464.x
Paper IV Enden T, Storaas T, Negaard A, Haig Y, Sandvik L, Gjesdal KI, Sandset PM, Kløw NE. Visualisation of the deep veins and detection of deep vein thrombosis with balanced TFE and contrast-enhanced T1 FFE using a blood pool agent. Submitted JMRI.