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Multimodal Percutaneous Intervention for Critical Venous Occlusive Disease
Multimodal Percutaneous Intervention for Critical Venous Occlusive Disease Rajeev Dayal, MD, Joshua Bernheim, MD, Daniel G. Clair, MD, Albeir Y. Mousa, MD, Scott Hollenbeck, MD, Brain DeRubertis, MD, James McKinsey, MD, Nicholas J. Morrissey, MD, K. Craig Kent, MD, and Peter L. Faries, MD, FACS, New York, New York
Critical deep venous thrombosis and occlusion constitutes a small percentage of patients with venous disease, who exhibit severe symptomatology. This study examined the results of multimodal percutaneous therapy for the treatment of complex critical venous thrombotic and occlusive disease. Twenty-five patients presented with critical venous thromboses or occlusions (11 with debilitating unilateral lower extremity edema causing ambulatory impairment, 2 with debilitating bilateral lower extremity edema, 3 with phlegmasia cerulea dolens, 2 with venous claudication, 2 with superior vena cava (SVS) syndrome with respiratory compromise, 4 with debilitating upper extremity edema, and 1 with renal insufficiency). Therapeutic modalities including thrombolysis, mechanical thrombectomy, percutaneous venoplasty and stent placement, temporary inferior vena cava filtration, and ultrasound guidance were used in all cases in conjunction with long-term systemic anticoagulation. The venous access site was determined by the anatomic location of the lesion and included popliteal, femoral, brachial, and lesser saphenous. Patients were followed with clinical exam and duplex surveillance. Resolution of symptoms was achieved in 18 of 25 patients (72%) and partial resolution occurred in 4 of 25 (16%). Failure of treatment identified as both lack of clinical response and evidence of continued venous thrombosis occurred 3 of 25 patients (12%). Restoration of arterial pulses and limb salvage was achieved in the three patients with phlegmasia cerulea dolens and acute limbthreatening ischemia. Both patients with SVC syndrome experienced resolution of respiratory compromise and facial edema. The mean length of follow-up was 11 ± 2.7 months. Complications included transfusion requirement (2), hematuria (2), retroperitoneal hematoma (1), and cellulitis (1). Acute critical venous thrombotic and occlusive disease is responsive to multimodal percutaneous treatment. The relief of pain and resolution of acutely life and limb-threatening conditions in this most severely symptomatic subset of patients represents the immediate goal of treatment.
INTRODUCTION Deep venous thrombosis (DVT) is a common disorder affecting 250,000 people in the United States per year. 1 Only a small percentage of individuals Department of Surgery, The New York-Presbyterian Hospital, Weill Medical College of Cornell University and Columbia College of Physicians and Surgeons, New York, NY, USA. Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004. Correspondence to: Peter L. Faries, MD, Department of Endovascular Surgery, Weill Medical College of Cornell University, Columbia University College of Physicians and Surgeons, The New York-Presbyterian Hospital, 525 E. 68th Street, Room P 705, New York, NY, 10021, USA, E-mail: [email protected] Ann Vasc Surg 2005; 19: 235-240 DOI: 10.1007/s10016-004-0167-6 Ó Annals of Vascular Surgery Inc. Published online: March 14, 2005
diagnosed with DVT progress to complications such as pulmonary embolism.2 However, the symptomatology associated with critical venous occlusive and thrombotic disorders is severe, and patients may develop life- and limb-threatening complications such as phlegmasia cerulea dolens or the superior vena cava (SVC) syndrome. While the use of thrombolysis for conventional DVT is controversial, standard medical and surgical therapy for critical venous occlusive and thrombotic disease is frequently inadequate. Systemic anticoagulation for venous occlusive disease relies on the patientÕs own thrombolytic systems to recanalize diseased segments and is successful in only 38% of cases of standard DVT.2 Surgical therapy consisting of thrombectomy with distal arteriovenous fistula creation is essentially 235
236 Dayal et al.
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Fig. 1. Initial venogram obtained from popliteal approach demonstrating thrombus within the popliteal vein (a), femoral vein, (b), and iliac vein (c).
reserved for ileofemoral DVT with impending venous gangrene, and even in these critical patients this therapy has been met with limited success.1 Systemic thrombolysis leads to complete resolution in a minority of patients and carries a 1-3% risk of intracranial hemorrhage.3 Recently, the use of endovascular techniques to reestablish patency for acute and chronic DVT has been described.1,4–9 This study describes the use of multiple percutaneous and minimally invasive methods for the treatment of critical venous occlusive and thrombotic disease.
METHODS Patients Institutional review board approval was obtained for this study. Patients were entered prospectively into a computerized database from July 2000 to December 2003. Twenty five patients experienced acute and chronic critical venous occlusive and thrombotic occlusions. Presenting symptoms included debilitating unilateral lower extremity edema (11 patients) debilitating bilateral lower extremity edema (2), phlegmasia cerulea dolens (3) venous claudication (2) SVC syndrome and respiratory compromise (2) debilitating upper extremity edema (4), and renal insufficiency (1). Patients with debilitating unilateral lower extremity edema received intervention only in the setting of severe ambulatory impairment to a distance of less than
one to two blocks. All patients had symptoms of less than 3 months duration, and 19 of 25 had symptoms of less than 6 weeks duration and were receiving standard anticoagulation regimens. Multiple therapeutic modalities were used in all cases in conjunction with long-term systemic anticoagulation. Endovascular Procedure Seventeen patients were treated in the operating room with portable imaging equipment (OEC 9800, GE Medical Systems, Milwaukee, WI) and 8 were treated in the angiography suite with fixed imaging systems (Siemens AG, Munich, Germany). Access site was determined by lesion location, and vessels were accessed via standard percutaneous approach with or without ultrasound guidance (Aloka, Wallingford, CT). Initial venograms were obtained to determine lesion location and lesion characteristics (Fig. 1). Lesions were then crossed using 0.035-inch glidewires (Terumo, Somerset, NJ). For thrombosis, treatments used included mechanical thrombectomy (AngioJet, Possis, Minneapolis, MN) and/or thrombolysis after placement of Mewissen (Boston Scientific, Natick, MA) thrombolysis catheters. Thrombolysis was performed by means of a pulse-spray technique with either urokinase (UK; Abbokinase, Abbott Laboratories, Chicago, IL) at an initial dose of 250,000 units followed by infusion of 120,000 units/hr or tissue plasminogen activator (Alteplase, tissue
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Multimodal percutaneous treatment of venous occlusion 237
Fig. 2. Venogram obtained after 72 hr of thrombolysis with urokinase demonstrating recanalized popliteal vein (a), femoral vein (b), and iliac vein (c).
plasminogen activator [TPA]; Genentech, San Francisco, CA) at an initial dose of 2 mg followed by continuous infusion of 0.5–1.5 mg/hr based on clot burden, severity of symptoms, and bleeding risk. Intravenous heparin was administered to maintain aPTT at 1.5 times control. All patients were observed in monitored settings and repeat venography was obtained 4–12 hr after the initial thrombolysis was begun. If thrombolysis resulted in complete resolution, the procedure was terminated (Fig. 2). If incomplete thrombolysis or an underlying lesion was noted, adjunctive therapies were then used consisting of additional thrombolysis, mechanical thrombectomy, transluminal venoplasty, or stent placement with self-expanding nitinol stents (Cordis, Warren, NJ). In all cases of continued thrombolysis, the patients returned for additional venography in 12–24 hr and if no improvement was seen by 96 hr, the procedure was terminated. As the duration of thrombolysis increased, the infused dose of thrombolytic agent was decreased after 48 hr to either 0.5mg/hr of TPA or 60,000 U/hr of UK to minimize bleeding complications. Outcomes and Patency Assessment Degree of thrombolysis was characterized according to the following grades: ‘‘complete’’ for 100% restoration of patency, ‘‘partial’’ for 50–99% luminal recovery, and ‘‘failure’’ for <50% luminal recovery
due to residual thrombus or stenosis. After intervention, patients were followed clinically and with ultrasound surveillance every 3 months. Duplex was used to assess for recurrent thrombosis, occlusion, or luminal narrowing >50%. Clinical success was defined as abatement or significant reduction in symptoms such as edema or pain, and partial success was defined as decrease in severity of symptoms but with documented recurrent thrombosis, occlusion, or restenosis by ultrasound. The clinical success rates, technical success rates, patency rates, and complication rates were expressed as percentages.
RESULTS Patients The mean age for the 25 patients was 48 ± 18 (range, 14–83) years and there were 11 females (44%) and 14 males (56%). Risk factors for development of DVT included malignancy (3), prior DVT (8), recent orthopedic operation (2), and recent abdominal operation (2). The most common presenting symptom was debilitating unlateral lower extremity edema; the remaining presenting symptoms are detailed in Table I. Endovascular Treatment The venous access site was determined by the anatomic location of the lesion and included pop-
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Table I. Presenting symptoms
Table II. Modality of treatment
Symptom
Patients (n = 25)
Unilateral lower extremity edema Bilateral lower extremity edema Phlegmasia cerulea dolens SVC syndrome Venous claudication Unilateral upper extremity edema Renal vein thrombosis
13 2 1 2 2 4 1
liteal (12, 2 bilateral), femoral (7), brachial (6), and lesser saphenous (2). Multiple therapeutic modalities were used in all cases (Table II) in conjunction with lifelong systemic anticoagulation in 24 of 25 cases. The average duration of thrombolysis was 45.9 ± 33.3 hr (range 0–96 hr). No increase in bleeding complications were noted for extended thrombolysis times, however, decreased doses were used in this situation. Mechanical thrombectomy was used as an adjunctive therapy in three cases to shorten the duration of thrombolysis. Underlying lesions in the inferior vena cava (IVC), subclavian, axillary, iliac, and femoral veins were treated by percutaneous transluminal venoplasty in 19 cases. Stenting was used for lesions resistant to angioplasty located in the subclavian, common iliac, external iliac, and proximal common and superficial femoral veins and was performed in 15 cases. An average of 3.16 ± 1.5 treatment modalities (range 1 to 5) were used per patient intervened upon. A flowchart depicting the treatment algorithm is detailed in Figure 3. Using these techniques, 100% luminal recovery was achieved in 15 of 25 (60%) patients and 50– 99% luminal recovery in 10 of 25 patients (40%). The mean length of follow-up was 11 ± 2.7 months, and 18 of 25 patients (72%) experienced overall clinical success for the duration of followup. Rates of clinical improvement were greater than rates of luminal recovery and appeared to be due to partial lumen recovery and restoration of flow. All six patients presenting with acute life- or limb-threatening conditions experienced resolution of symptoms. Restoration of arterial pulses and limb salvage were achieved in the three patients with phlegmasia cerulea dolens and acute limbthreatening ischemia. Both patients with SVC syndrome experienced resolution of respiratory compromise and facial edema. The patient with renal vein thrombosis recovered normal renal function. Seven of 11 patients with debilitating unilateral lower extremity edema achieved relief of
Modality of treatment
n
Thrombolysis Mechanical thrombectomy Transluminal venoplasty Stent placement Retrievable IVC filter Ultrasound guidance Total
20 3 19 15 3 15 75
Fig. 3. Flowchart of treatment algorithm.
symptoms, 2 of 2 with debilitating bilateral lower extremity edema achieved relief of symptoms, zero of 2 patients with venous claudication achieved relief of symptoms, and 3 of 4 patients with debilitating upper extremity edema achieved relief of symptoms. There was one early failure within 14 days in a patient who initially had complete angiographic resolution. This patient presented with subclavian vein thrombosis treated by thrombolysis, transluminal venoplasty, and stent placement for upper extremity edema. This was the only patient in this group with chronic renal failure on hemodialysis with an upper extremity arteriovenous graft that had developed chronic outflow obstruction. Stents were placed in the subclavian (1), innominate (2), common iliac (3), external iliac (4), common femoral (2), and superficial femoral veins (3). Duplex surveillance revealed that 13 of 25 patients (48%) developed recurrent occlusions or thrombosis; however, clinical improvement was maintained in 5 despite evidence of recurrent stenosis or thrombosis (Fig. 4). By duplex examination, stent patency was maintained in all stents in the common femoral and innominate vein, and in two of four stents in the external iliac vein. All four patients who received stents in the superficial
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Multimodal percutaneous treatment of venous occlusion 239
Table III. Stent patency by site of placement
Fig. 4. Kaplan-Meier graph depicting patency documented by surveillance duplex examinations versus clinical symptom relief.
femoral veins and subclavian vein demonstrated occlusion within 3 months of stent placement (Table III). The overall complication rate was 6 of 25 and included transfusion requirement (2), hematuria (2), retroperitoneal hematoma (1), and cellulitis (1). Bleeding complications occurred with similar frequency in patients who received short and long courses of thrombolysis.
DISCUSSION This report summarizes our experience using percutaneous interventions for critical venous occlusive disease. Multiple modalities were used to provide symptomatic relief to this subset of patients with advanced presentations including life- and limb-threatening symptoms. The relief of symptoms in the immediate postintervention period was achieved in a majority of patients (72%), despite recurrent thrombosis or occlusions demonstrated by duplex ultrasound (48%) in patients followed for the duration of the study. The mechanism for continued relief despite recurrent pathology is uncertain but may relate to partial lumen recovery and immediate restoration of flow, allowing time for the development of collateral pathways for venous return. The primary method of vessel access was via the popliteal vein ipsilateral to the thrombus or occlusion, which was accessed under ultrasound guidance. This reflected the fact that a majority of patients presented with lower extremity and iliac lesions. The ipsilateral popliteal vein approach allows for easier traversal of popliteal, femoral, and iliac vein lesions with potential to treat thrombi in the IVC as well. The only potential drawback to using the popliteal vein approach is potential bleeding due to passing the cannulation needle into surrounding vessels, therefore this procedure
Site
Patency
Innominate vein Subclavian vein Common iliac vein External iliac vein Common femoral vein Superficial femoral vein
100% 100% 100% 50% 100% 0%
(2/2) (1/1) (3/3) (2/4) (2/2) (0/3)
must be done carefully under ultrasound guidance. Mechanical thrombectomy was used in select situations of acute thrombosis with large clot burden to allow for potentially shorter duration of thrombolysis. Balloon angioplasty was used selectively for underlying lesions followed by stenting for residual stenoses. Over the period of observation, all stents placed in the subclavian vein and superficial femoral veins occluded, whereas in the remaining positions only one stent occluded and was located in the external iliac vein. This led to a decrease in the use of stents in the superficial femoral veins for the remainder of the study, finding similar to those in other studies.4,10 There have been reports of fatal and nonfatal pulmonary embolism while performing thrombolysis4,3,11,12,, thus IVC filtration was used routinely for patients with extensive thrombus of the IVC in this study. As a result, eight patients in this study received permanent IVC filters because of extensive thrombus in the IVC. Retrievable filters were reserved for the situation where thrombus was seen to extend through a prior placed IVC filter, and consequently, retrievable IVC filters were placed in three patients in this study. The standard treatment for uncomplicated DVT remains systemic anticoagulation with intravenous heparin or a low-molecular-weight heparinoid followed by 3 to 6 months of oral warfarin.2 Despite multiple studies to examine the potential benefit of systemic and catheter-directed thrombolysis3,4,13 there is still debate regarding its use for uncomplicated DVT. However, in the situation of severe symptomatology, standard therapy with systemic anticoagulation may be inadequate. For that reason, our study is limited to those patients with severe debilitating symptoms and life- or limbthreatening findings. In a report of the national venous registry, Mewissen et al. reported the outcomes of patients diagnosed with symptomatic DVT treated with catheter directed thrombolysis and concluded that catheter-directed thrombolysis is
240 Dayal et al.
both safe and effective with an overall complication rate of 11%.4 A positive correlation was noted between initial degree of thrombolysis and long-term patency, which our study was unable to detect, perhaps because an inadequate number of patients were enrolled in our study. The overall major hemorrhagic complication rate was 12% (3/25), specifically transfusion requirement (2) and retroperitoneal hematoma (1), thus emphasizing the fact that these therapies are not without risk.14 This complication rate is similar to rates reported in other studies and underscores the notion that these therapies should be reserved for patients with severe symptoms.3,4 However, despite these risks, percutaneous therapies appear to represent the least morbid and most successful method of treating patients with severe venous occlusive disease.
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2. 3.
4.
5.
6.
7.
8.
CONCLUSIONS Acute critical venous thrombotic and occlusive disease is responsive to multimodal percutaneous treatment including thrombomechanical recanalization, thrombolysis, venoplasty, stent placement, and anticoagulation. Immediate symptomatic relief of pain and massive edema as well as resolution of acutely life- and limb-threatening conditions in this subset of patients represents the goal of treatment. The relief of symptoms can persist despite demonstration of rethrombosis or occlusion on duplex surveillance. The impact of multimodal therapy on the subsequent development of chronic venous complications including post-thrombotic syndrome remains to be defined.
9.
10.
11.
12.
13.
14.
REFERENCES 1. Sharafuddin MJ, Sun S, Hoballah JJ, Youness FM, Sharp WJ, Roh BS. Endovascular management of venous throm-
botic, occlusive diseases of the lower extremitites. J Vase Interv Radiol 2003;14:405-423. Kearon C. Natural history of venous thromboembolism. 2003;107:I-22-I30. Schweizer J, Kirch W, Koch R, et al. Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol 2000;36:1336-1343. Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology 1999;211:39-49. Verhaeghe R, Maleux G. Endovascular local thrombolytic therapy of ileofemoral and inferior caval vein thrombosis. Semin Vasc Med 2001;1:123-127. Vedantham S, Vesely TM, Sicard GA, et al. Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein thrombosis. J Vase Interv Radiol 2004;15:565-574. Vedantham S, Vesely TM, Parti N, Darcy M, Hovsepian DM, Picus D. Lower extremity venous thrombolysis with adjunctive mechanical thrombectomy. J Vasc Interv Radiol 2002;13:1001-1008. Kasirajan K, Gray B, Ouriel K. Percutaneous Angiojet thrombectomy in the management of extensive deep venous thrombosis. J Vasc Interv Radiol 2001;12:179-185. Bjarnason H, Kruse JR, Asinger DA, et al. Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 1997;8:405-418. Ley EJ, Hood DB, Leke MA, Rao RK, Rowe VL, Weaver FA. Endovascular management of iliac vein occlusive disease. Ann Vase Surg 2004;18:228-233. Tarry WC, Makhoul RG, Tisnado J, Posner MP, Sobel M, Lee HM. Catheter-directed thrombolysis following vena cava filtration for severe deep venous thrombosis. Ann Vasc Surg 1994;8:583-590. Yamagami T, Kato T, Iida S, Tanaka O, Nishimura T. Retrievable vena cava filter placement during treatment for deep venous thrombosis. Br J Radiol 2003;76:712-718. Grunwald MR, Hofmann LV. Comparison of urokinase, alteplase, and reteplase for catheter-directed thrombolysis of deep venous thrombosis. J Vasc Interv Radiol 2004;15:347352. Sugimoto K, Hofmann LV, Razavi MK, et al. The safety, efficacy, and pharmacoeconomics of low-dose alteplase compared with urokinase for catheter-directed thrombolysis of arterial and venous occlusions. J Vasc Surg 2003;37:512517.
Critical deep venous thrombosis and occlusion constitutes a small percentage of patients with venous disease, who exhibit severe symptomatology. This study examined the results of multimodal percutaneous therapy for the treatment of complex critical venous thrombotic and occlusive disease. Twenty-five patients presented with critical venous thromboses or occlusions (11 with debilitating unilateral lower extremity edema causing ambulatory impairment, 2 with debilitating bilateral lower extremity edema, 3 with phlegmasia cerulea dolens, 2 with venous claudication, 2 with superior vena cava (SVS) syndrome with respiratory compromise, 4 with debilitating upper extremity edema, and 1 with renal insufficiency). Therapeutic modalities including thrombolysis, mechanical thrombectomy, percutaneous venoplasty and stent placement, temporary inferior vena cava filtration, and ultrasound guidance were used in all cases in conjunction with long-term systemic anticoagulation. The venous access site was determined by the anatomic location of the lesion and included popliteal, femoral, brachial, and lesser saphenous. Patients were followed with clinical exam and duplex surveillance. Resolution of symptoms was achieved in 18 of 25 patients (72%) and partial resolution occurred in 4 of 25 (16%). Failure of treatment identified as both lack of clinical response and evidence of continued venous thrombosis occurred 3 of 25 patients (12%). Restoration of arterial pulses and limb salvage was achieved in the three patients with phlegmasia cerulea dolens and acute limbthreatening ischemia. Both patients with SVC syndrome experienced resolution of respiratory compromise and facial edema. The mean length of follow-up was 11 ± 2.7 months. Complications included transfusion requirement (2), hematuria (2), retroperitoneal hematoma (1), and cellulitis (1). Acute critical venous thrombotic and occlusive disease is responsive to multimodal percutaneous treatment. The relief of pain and resolution of acutely life and limb-threatening conditions in this most severely symptomatic subset of patients represents the immediate goal of treatment.
INTRODUCTION Deep venous thrombosis (DVT) is a common disorder affecting 250,000 people in the United States per year. 1 Only a small percentage of individuals Department of Surgery, The New York-Presbyterian Hospital, Weill Medical College of Cornell University and Columbia College of Physicians and Surgeons, New York, NY, USA. Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004. Correspondence to: Peter L. Faries, MD, Department of Endovascular Surgery, Weill Medical College of Cornell University, Columbia University College of Physicians and Surgeons, The New York-Presbyterian Hospital, 525 E. 68th Street, Room P 705, New York, NY, 10021, USA, E-mail: [email protected] Ann Vasc Surg 2005; 19: 235-240 DOI: 10.1007/s10016-004-0167-6 Ó Annals of Vascular Surgery Inc. Published online: March 14, 2005
diagnosed with DVT progress to complications such as pulmonary embolism.2 However, the symptomatology associated with critical venous occlusive and thrombotic disorders is severe, and patients may develop life- and limb-threatening complications such as phlegmasia cerulea dolens or the superior vena cava (SVC) syndrome. While the use of thrombolysis for conventional DVT is controversial, standard medical and surgical therapy for critical venous occlusive and thrombotic disease is frequently inadequate. Systemic anticoagulation for venous occlusive disease relies on the patientÕs own thrombolytic systems to recanalize diseased segments and is successful in only 38% of cases of standard DVT.2 Surgical therapy consisting of thrombectomy with distal arteriovenous fistula creation is essentially 235
236 Dayal et al.
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Fig. 1. Initial venogram obtained from popliteal approach demonstrating thrombus within the popliteal vein (a), femoral vein, (b), and iliac vein (c).
reserved for ileofemoral DVT with impending venous gangrene, and even in these critical patients this therapy has been met with limited success.1 Systemic thrombolysis leads to complete resolution in a minority of patients and carries a 1-3% risk of intracranial hemorrhage.3 Recently, the use of endovascular techniques to reestablish patency for acute and chronic DVT has been described.1,4–9 This study describes the use of multiple percutaneous and minimally invasive methods for the treatment of critical venous occlusive and thrombotic disease.
METHODS Patients Institutional review board approval was obtained for this study. Patients were entered prospectively into a computerized database from July 2000 to December 2003. Twenty five patients experienced acute and chronic critical venous occlusive and thrombotic occlusions. Presenting symptoms included debilitating unilateral lower extremity edema (11 patients) debilitating bilateral lower extremity edema (2), phlegmasia cerulea dolens (3) venous claudication (2) SVC syndrome and respiratory compromise (2) debilitating upper extremity edema (4), and renal insufficiency (1). Patients with debilitating unilateral lower extremity edema received intervention only in the setting of severe ambulatory impairment to a distance of less than
one to two blocks. All patients had symptoms of less than 3 months duration, and 19 of 25 had symptoms of less than 6 weeks duration and were receiving standard anticoagulation regimens. Multiple therapeutic modalities were used in all cases in conjunction with long-term systemic anticoagulation. Endovascular Procedure Seventeen patients were treated in the operating room with portable imaging equipment (OEC 9800, GE Medical Systems, Milwaukee, WI) and 8 were treated in the angiography suite with fixed imaging systems (Siemens AG, Munich, Germany). Access site was determined by lesion location, and vessels were accessed via standard percutaneous approach with or without ultrasound guidance (Aloka, Wallingford, CT). Initial venograms were obtained to determine lesion location and lesion characteristics (Fig. 1). Lesions were then crossed using 0.035-inch glidewires (Terumo, Somerset, NJ). For thrombosis, treatments used included mechanical thrombectomy (AngioJet, Possis, Minneapolis, MN) and/or thrombolysis after placement of Mewissen (Boston Scientific, Natick, MA) thrombolysis catheters. Thrombolysis was performed by means of a pulse-spray technique with either urokinase (UK; Abbokinase, Abbott Laboratories, Chicago, IL) at an initial dose of 250,000 units followed by infusion of 120,000 units/hr or tissue plasminogen activator (Alteplase, tissue
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Multimodal percutaneous treatment of venous occlusion 237
Fig. 2. Venogram obtained after 72 hr of thrombolysis with urokinase demonstrating recanalized popliteal vein (a), femoral vein (b), and iliac vein (c).
plasminogen activator [TPA]; Genentech, San Francisco, CA) at an initial dose of 2 mg followed by continuous infusion of 0.5–1.5 mg/hr based on clot burden, severity of symptoms, and bleeding risk. Intravenous heparin was administered to maintain aPTT at 1.5 times control. All patients were observed in monitored settings and repeat venography was obtained 4–12 hr after the initial thrombolysis was begun. If thrombolysis resulted in complete resolution, the procedure was terminated (Fig. 2). If incomplete thrombolysis or an underlying lesion was noted, adjunctive therapies were then used consisting of additional thrombolysis, mechanical thrombectomy, transluminal venoplasty, or stent placement with self-expanding nitinol stents (Cordis, Warren, NJ). In all cases of continued thrombolysis, the patients returned for additional venography in 12–24 hr and if no improvement was seen by 96 hr, the procedure was terminated. As the duration of thrombolysis increased, the infused dose of thrombolytic agent was decreased after 48 hr to either 0.5mg/hr of TPA or 60,000 U/hr of UK to minimize bleeding complications. Outcomes and Patency Assessment Degree of thrombolysis was characterized according to the following grades: ‘‘complete’’ for 100% restoration of patency, ‘‘partial’’ for 50–99% luminal recovery, and ‘‘failure’’ for <50% luminal recovery
due to residual thrombus or stenosis. After intervention, patients were followed clinically and with ultrasound surveillance every 3 months. Duplex was used to assess for recurrent thrombosis, occlusion, or luminal narrowing >50%. Clinical success was defined as abatement or significant reduction in symptoms such as edema or pain, and partial success was defined as decrease in severity of symptoms but with documented recurrent thrombosis, occlusion, or restenosis by ultrasound. The clinical success rates, technical success rates, patency rates, and complication rates were expressed as percentages.
RESULTS Patients The mean age for the 25 patients was 48 ± 18 (range, 14–83) years and there were 11 females (44%) and 14 males (56%). Risk factors for development of DVT included malignancy (3), prior DVT (8), recent orthopedic operation (2), and recent abdominal operation (2). The most common presenting symptom was debilitating unlateral lower extremity edema; the remaining presenting symptoms are detailed in Table I. Endovascular Treatment The venous access site was determined by the anatomic location of the lesion and included pop-
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Table I. Presenting symptoms
Table II. Modality of treatment
Symptom
Patients (n = 25)
Unilateral lower extremity edema Bilateral lower extremity edema Phlegmasia cerulea dolens SVC syndrome Venous claudication Unilateral upper extremity edema Renal vein thrombosis
13 2 1 2 2 4 1
liteal (12, 2 bilateral), femoral (7), brachial (6), and lesser saphenous (2). Multiple therapeutic modalities were used in all cases (Table II) in conjunction with lifelong systemic anticoagulation in 24 of 25 cases. The average duration of thrombolysis was 45.9 ± 33.3 hr (range 0–96 hr). No increase in bleeding complications were noted for extended thrombolysis times, however, decreased doses were used in this situation. Mechanical thrombectomy was used as an adjunctive therapy in three cases to shorten the duration of thrombolysis. Underlying lesions in the inferior vena cava (IVC), subclavian, axillary, iliac, and femoral veins were treated by percutaneous transluminal venoplasty in 19 cases. Stenting was used for lesions resistant to angioplasty located in the subclavian, common iliac, external iliac, and proximal common and superficial femoral veins and was performed in 15 cases. An average of 3.16 ± 1.5 treatment modalities (range 1 to 5) were used per patient intervened upon. A flowchart depicting the treatment algorithm is detailed in Figure 3. Using these techniques, 100% luminal recovery was achieved in 15 of 25 (60%) patients and 50– 99% luminal recovery in 10 of 25 patients (40%). The mean length of follow-up was 11 ± 2.7 months, and 18 of 25 patients (72%) experienced overall clinical success for the duration of followup. Rates of clinical improvement were greater than rates of luminal recovery and appeared to be due to partial lumen recovery and restoration of flow. All six patients presenting with acute life- or limb-threatening conditions experienced resolution of symptoms. Restoration of arterial pulses and limb salvage were achieved in the three patients with phlegmasia cerulea dolens and acute limbthreatening ischemia. Both patients with SVC syndrome experienced resolution of respiratory compromise and facial edema. The patient with renal vein thrombosis recovered normal renal function. Seven of 11 patients with debilitating unilateral lower extremity edema achieved relief of
Modality of treatment
n
Thrombolysis Mechanical thrombectomy Transluminal venoplasty Stent placement Retrievable IVC filter Ultrasound guidance Total
20 3 19 15 3 15 75
Fig. 3. Flowchart of treatment algorithm.
symptoms, 2 of 2 with debilitating bilateral lower extremity edema achieved relief of symptoms, zero of 2 patients with venous claudication achieved relief of symptoms, and 3 of 4 patients with debilitating upper extremity edema achieved relief of symptoms. There was one early failure within 14 days in a patient who initially had complete angiographic resolution. This patient presented with subclavian vein thrombosis treated by thrombolysis, transluminal venoplasty, and stent placement for upper extremity edema. This was the only patient in this group with chronic renal failure on hemodialysis with an upper extremity arteriovenous graft that had developed chronic outflow obstruction. Stents were placed in the subclavian (1), innominate (2), common iliac (3), external iliac (4), common femoral (2), and superficial femoral veins (3). Duplex surveillance revealed that 13 of 25 patients (48%) developed recurrent occlusions or thrombosis; however, clinical improvement was maintained in 5 despite evidence of recurrent stenosis or thrombosis (Fig. 4). By duplex examination, stent patency was maintained in all stents in the common femoral and innominate vein, and in two of four stents in the external iliac vein. All four patients who received stents in the superficial
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Multimodal percutaneous treatment of venous occlusion 239
Table III. Stent patency by site of placement
Fig. 4. Kaplan-Meier graph depicting patency documented by surveillance duplex examinations versus clinical symptom relief.
femoral veins and subclavian vein demonstrated occlusion within 3 months of stent placement (Table III). The overall complication rate was 6 of 25 and included transfusion requirement (2), hematuria (2), retroperitoneal hematoma (1), and cellulitis (1). Bleeding complications occurred with similar frequency in patients who received short and long courses of thrombolysis.
DISCUSSION This report summarizes our experience using percutaneous interventions for critical venous occlusive disease. Multiple modalities were used to provide symptomatic relief to this subset of patients with advanced presentations including life- and limb-threatening symptoms. The relief of symptoms in the immediate postintervention period was achieved in a majority of patients (72%), despite recurrent thrombosis or occlusions demonstrated by duplex ultrasound (48%) in patients followed for the duration of the study. The mechanism for continued relief despite recurrent pathology is uncertain but may relate to partial lumen recovery and immediate restoration of flow, allowing time for the development of collateral pathways for venous return. The primary method of vessel access was via the popliteal vein ipsilateral to the thrombus or occlusion, which was accessed under ultrasound guidance. This reflected the fact that a majority of patients presented with lower extremity and iliac lesions. The ipsilateral popliteal vein approach allows for easier traversal of popliteal, femoral, and iliac vein lesions with potential to treat thrombi in the IVC as well. The only potential drawback to using the popliteal vein approach is potential bleeding due to passing the cannulation needle into surrounding vessels, therefore this procedure
Site
Patency
Innominate vein Subclavian vein Common iliac vein External iliac vein Common femoral vein Superficial femoral vein
100% 100% 100% 50% 100% 0%
(2/2) (1/1) (3/3) (2/4) (2/2) (0/3)
must be done carefully under ultrasound guidance. Mechanical thrombectomy was used in select situations of acute thrombosis with large clot burden to allow for potentially shorter duration of thrombolysis. Balloon angioplasty was used selectively for underlying lesions followed by stenting for residual stenoses. Over the period of observation, all stents placed in the subclavian vein and superficial femoral veins occluded, whereas in the remaining positions only one stent occluded and was located in the external iliac vein. This led to a decrease in the use of stents in the superficial femoral veins for the remainder of the study, finding similar to those in other studies.4,10 There have been reports of fatal and nonfatal pulmonary embolism while performing thrombolysis4,3,11,12,, thus IVC filtration was used routinely for patients with extensive thrombus of the IVC in this study. As a result, eight patients in this study received permanent IVC filters because of extensive thrombus in the IVC. Retrievable filters were reserved for the situation where thrombus was seen to extend through a prior placed IVC filter, and consequently, retrievable IVC filters were placed in three patients in this study. The standard treatment for uncomplicated DVT remains systemic anticoagulation with intravenous heparin or a low-molecular-weight heparinoid followed by 3 to 6 months of oral warfarin.2 Despite multiple studies to examine the potential benefit of systemic and catheter-directed thrombolysis3,4,13 there is still debate regarding its use for uncomplicated DVT. However, in the situation of severe symptomatology, standard therapy with systemic anticoagulation may be inadequate. For that reason, our study is limited to those patients with severe debilitating symptoms and life- or limbthreatening findings. In a report of the national venous registry, Mewissen et al. reported the outcomes of patients diagnosed with symptomatic DVT treated with catheter directed thrombolysis and concluded that catheter-directed thrombolysis is
240 Dayal et al.
both safe and effective with an overall complication rate of 11%.4 A positive correlation was noted between initial degree of thrombolysis and long-term patency, which our study was unable to detect, perhaps because an inadequate number of patients were enrolled in our study. The overall major hemorrhagic complication rate was 12% (3/25), specifically transfusion requirement (2) and retroperitoneal hematoma (1), thus emphasizing the fact that these therapies are not without risk.14 This complication rate is similar to rates reported in other studies and underscores the notion that these therapies should be reserved for patients with severe symptoms.3,4 However, despite these risks, percutaneous therapies appear to represent the least morbid and most successful method of treating patients with severe venous occlusive disease.
Annals of Vascular Surgery
2. 3.
4.
5.
6.
7.
8.
CONCLUSIONS Acute critical venous thrombotic and occlusive disease is responsive to multimodal percutaneous treatment including thrombomechanical recanalization, thrombolysis, venoplasty, stent placement, and anticoagulation. Immediate symptomatic relief of pain and massive edema as well as resolution of acutely life- and limb-threatening conditions in this subset of patients represents the goal of treatment. The relief of symptoms can persist despite demonstration of rethrombosis or occlusion on duplex surveillance. The impact of multimodal therapy on the subsequent development of chronic venous complications including post-thrombotic syndrome remains to be defined.
9.
10.
11.
12.
13.
14.
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