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Commencing Volume 19, Issue 1, MedReviews has ceased the publication of this journal. Reviews in Cardiovascular Medicine will continue to be published by IMRPress, Ltd. (www.imrpress.org)

Volume 3, Supplement 2, 2002

Volume 3, Supplement 2, 2002

Table of Contents

Comparison of Surgical and Thrombolytic Treatment of Peripheral Arterial Disease
Acute occlusion of a peripheral artery is a catastrophic event. Whether resulting from in situ thrombosis of a native artery, a bypass graft, or embolization, acute limb ischemia threatens both the patient’s limb and life. Traditionally, open surgical intervention has been the “gold standard” for treatment of these patients. However, the multiplicity and complexity of medical comorbidities account for high rates of perioperative morbidity and mortality. Thus, a minimally invasive alternative to open surgery is desirable, provided that the rate of limb salvage remains similar and other untoward events are infrequent. Catheter-directed thrombolytic therapy has been studied in this regard, offering the potential to restore arterial perfusion without the need for open surgery in many cases. In addition, thrombolysis can clear thrombus from small arteries that are inaccessible to a balloon catheter. Lastly, successful thrombolysis may unmask the lesion responsible for the occlusion and allow a directed, sometimes less invasive treatment. Thrombolysis has been criticized, however, on the basis of associated hemorrhagic complications, a slow rate of thrombus dissolution, and a higher risk of rethrombosis. This article explores the available data and, in this manner, provides an analysis of open surgery and thrombolytic therapy as initial interventions in patients with lower limb ischemia. [Rev Cardiovasc Med. 2002;3(suppl 2):S7–S16]
Therapeutic Agents- Pharmacokinetics and Pharmacodynamics
Various thrombolytic agents have been studied as activators of the plasminogen-plasmin system for thrombolysis of thrombus formation. They include streptokinase, urokinase, tissue plasminogen activators, single-chain urokinase plasminogen activator, and anisoylated or acylated plasminogen-streptokinase activator complex (APSAC), only some of which are commercially available. All thrombolytic agents, including APSAC (not commercially available), recombinant tissue plasminogen activator, and prourokinase, generate great quantities of degradation products of fibrinogen or fibrin. All of the second-generation thrombolytic agents induce systemic activation of the entire fibrinolytic system, and none are capable of specifically activating the fibrinolytic system at the site of thrombus formation. The most systemically active agent known at the present time is APSAC. Trials show that bleeding occurs as frequently with the second-generation agents as with the older agents, and further studies may even find that the newer agents are associated with more bleeding than urokinase and streptokinase have been. With knowledge of the properties of the various thrombolytic agents available today, the physician can intelligently select the optimal agent for a given patient problem. [Rev Cardiovasc Med. 2002;3(suppl 2):S34–S44]
Thrombolytic Therapy for Acute Deep Vein Thrombosis and the Venous Registry
Randomized clinical trials have defined anticoagulation with unfractionated or low molecular weight heparin followed by warfarin as standard therapy for acute deep venous thrombosis (DVT). Such treatment is highly effective in preventing recurrent venous thromboembolism, but provides imperfect protection against development of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, catheter-directed thrombolytic therapy potentially affords an improved long-term outcome in selected patients with DVT. A national venous registry, compiling data from 63 participating centers, was established to collect data regarding the technical details of the procedure and early outcome. Data from the registry have established the optimal technical approach and patient population. An antegrade catheter-directed approach using urokinase in patients with acute iliofemoral DVT of less than 10 days duration and no prior history of DVT may achieve complete lysis in 65% of patients. Analysis of the clinical outcome is pending, but early results suggest improved valve function and fewer symptoms at 1 year in patients with complete thrombolysis. These promising data should serve as the basis for future randomized trials of catheterdirected thrombolysis for the treatment of acute DVT. [Rev Cardiovasc Med. 2002;3(suppl 2):S53–S60]
Quality-of-Life Improvement Using Thrombolytic Therapy for Iliofemoral Deep Venous Thrombosis
Patients with iliofemoral deep venous thrombosis suffer the most severe postthrombotic morbidity. Techniques that effectively remove thrombus from the venous system eliminate venous obstruction and potentially preserve valvular function. This will likely reduce or avoid the postthrombotic syndrome and improve long-term quality of life. To evaluate whether catheter-directed thrombolysis is associated with improved quality of life compared with anticoagulation alone and whether outcome in the thrombolysis group is related to lytic success, 98 patients with iliofemoral deep venous thrombosis who were treated at least 6 months earlier were identified and queried with a validated health-related quality-of-life questionnaire. Sixtyeight patients were identified through the Venous Registry (a national, multicenter venous registry) and were treated with catheter-directed thrombolysis with urokinase, and 30 patients were identified by means of medical record review and were treated with anticoagulation alone. All patients were candidates for thrombolysis; however, the treatment decision was made according to physician preference. The two treatment groups did not differ significantly in average time between the reference hospitalization and first contact. No difference was found in physical functioning and well-being between the groups before the development of deep venous thrombosis. Following treatment, patients receiving catheter-directed thrombolysis reported better overall physical functioning, less stigma, less health distress, and fewer postthrombotic symptoms compared to those patients treated with anticoagulation alone. Within the thrombolysis group, successful lysis correlated with health-related quality of life. Catheter-directed thrombolysis for the management of patients with iliofemoral deep venous thrombosis significantly improves health-related quality of life compared to similar patients treated with anticoagulation alone. Improved quality of life is related to successful thrombolysis. These data offer a compelling argument for a prospective randomized study. [Rev Cardiovasc Med. 2002;3(suppl 2):S61–S67]
Pulmonary Embolism
The natural history of pulmonary embolism (PE) is incompletely characterized, because most episodes of PE go undetected, the clinical presentation mimics so many other common and uncommon diseases, the sensitivity and specificity of the diagnostic tests are poorly defined, and even detection at autopsy is difficult and requires close examination of the pulmonary arteries. Yet PE is a significant cause of morbidity and mortality in the hospitalized patient, and one reason for its extremely high incidence is the failure of physicians to provide adequate prophylaxis to patients who are at risk of developing venous thromboembolism. The mortality rate for PE is less than 8% when the condition is recognized and treated correctly but approximately 30% when untreated. Pulmonary arteriography is still the gold standard in diagnosing pulmonary emboli, but several other imaging modalities have been used to diagnose pulmonary emboli in recent years, including transthoracic and transesophageal echocardiography, magnetic resonance angiography, spiral computerized tomography, and ventilation-perfusion lung scanning. The treatment modality chosen depends directly on the clinical presentation of the patient. Low molecular weight heparin may be equal or superior in efficacy to unfractionated heparin for the treatment of deep venous thrombosis and PE. Thrombolytic therapy can be considered for patients with hemodynamic instability, those with right ventricular dysfunction, and young patients with a massive PE despite a normal right ventricle on echocardiography. In those patients who cannot receive anticoagulation therapy or thrombolysis, or who remain at high risk, an inferior vena cava filter should be placed. [Rev Cardiovasc Med. 2002;3(suppl 2):S68–S75]
Thrombolysis for the Treatment of Thrombosed Hemodialysis Access Grafts
Maintaining the patency of hemodialysis access grafts remains problematic. It is best to recognize the failing graft prior to its thrombosis by noting an increase in recirculation, decreased flow (as measured by a Transonics device), changes in Doppler ultrasound findings, elevation of venous pressures, or swelling of the arm. If a failing graft is suspected, an angiogram should be performed to evaluate the graft. If a problem is identified it should be corrected. If it is a graft thrombosis, it can be opened using percutaneous techniques. Percutaneous declotting has been evolving since its introduction in the early 1980s. At first, a low-dose thrombolytic infusion through a single catheter was used. Crossing catheters with a higher-dose infusion was then introduced. Finally, pharmacomechanical thrombolysis, which used crossing catheters and a pulse-spray technique, became popular. Several mechanical devices have proven to be efficacious as well. In 1997, we described the “lyseand- wait” technique. We believe “lyse and wait” to be a simpler and quicker technique, and its initial success has been similar to that for the previously described techniques. After the graft is successfully declotted, the arterial plug must be mobilized and the stenotic lesion must be addressed either by angioplasty, stent placement, surgery, or any combination of these interventions. [Rev Cardiovasc Med. 2002;3(suppl 2):S84–S91]