Deep venous thrombosis after radiofrequency ablation of greater saphenous vein: A word of caution

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1 From the American Venous Forum Deep venous thrombosis after radiofrequency ablation of greater saphenous vein: A word of caution Anil P. Hingorani, MD, Enrico Ascher, MD, Natalia Markevich, MD, RVT, Richard W. Schutzer, MD, Sreedhar Kallakuri, MD, Alexander Hou, MD, Suresh Nahata, MD, William Yorkovich, RPA, and Theresa Jacob, PhD, Brooklyn, NY Purpose: Radiofrequency ablation (RFA) of the greater saphenous vein (GSV; closure ) is a relatively new option for treatment of venous reflux. However, our initial enthusiasm for this minimally invasive technique has been tempered by our preliminary experience with its potentially lethal complication, deep venous thrombosis (DVT). Methods: Seventy-three lower extremities were treated in 66 patients with GSV reflux, between April 2003 and February There were 48 (73%) female patients and 18 (27%) male patients, with ages ranging from 26 to 88 years (mean, years). RFA was combined with stab avulsion of varicosities in 55 (75%) patients and subfascial ligation of perforator veins in 6 (8%) patients. An ATL HDI 5000 scanner with linear 7-4 MHz probe and the SonoCT feature was used for GSV mapping and procedure guidance in all procedures. GSV diameter determined the size of the RFA catheter used. Veins less than 8 mm in diameter were treated with a 6F catheter (n 54); an 8F catheter was used for veins greater than 8 mm in diameter (n 19). The GSV was cannulated at the knee level. The tip of the catheter was positioned within 1 cm of the origin of the inferior epigastric vein (first GSV tributary). All procedures were carried out according to manufacturer guidelines. Results: All patients underwent venous duplex ultrasound scanning 2 to 30 days (mean, 10 6 days) after the procedure. The duplex scans documented occlusion of the GSV in 70 limbs (96%). In addition, DVT was found in 12 limbs (16%). Eleven patients (92%) had an extension of the occlusive clot filling the treated proximal GSV segment, with a floating tail beyond the patent inferior epigastric vein into the common femoral vein. Another patient developed acute occlusive clots in the calf muscle (gastrocnemius) veins. Eight patients were readmitted and received anticoagulation therapy. Four patients were treated with enoxaparin on an ambulatory basis. None of these patients had pulmonary embolism. Initially 3 patients with floating common femoral vein clots underwent inferior vena cava filter placement. Of the 19 limbs treated with the 8F RFA catheter, GSV clot extension developed in 5 (26%), compared with 7 of 54 (13%) limbs treated with the 6F RFA catheter (P.3). No difference was found between the occurrence of DVT in patients who underwent the combined procedure (RFA and varicose vein excision) compared with patients who underwent GSV RFA alone (P.7). No statistically significant differences were found in age or gender of patients with or without postoperative DVT (P NS). Conclusion: Patients who underwent combined GSV RFA and varicose vein excision did not demonstrate a higher occurrence of postoperative DVT compared with patients who underwent RFA alone. Early postoperative duplex scans are essential, and should be mandatory in all patients undergoing RFA of the GSV. (J Vasc Surg 2004;40:500-4.) Venous insufficiency is one of the most common problems in all of medicine. 1-5 One of the standard treatments has been high ligation with proximal stripping of the greater saphenous vein (GSV). 6,7 However, significant morbidity, dissatisfaction, and rate of recurrence have been documented with this procedure As an alternative, radiofrequency ablation (RFA) of the GSV ( Closure ) has been introduced as a relatively new option for treatment of venous reflux. The procedure is From the Division of Vascular Surgery, Maimonides Medical Center. Presented at the Sixteenth Annual Meeting of the American Venous Forum, Kissimmee, Fla, Feb 26-29, Competition of interest: none. Reprint requests: Anil Hingorani, MD, Maimonides Medical Center, Division of Vascular Surgery, th Ave, Brooklyn, NY ( ahingorani@maimonidesmed.org) /$30.00 Copyright 2004 by The Society for Vascular Surgery. doi: /j.jvs minimally invasive, simple, associated with decreased pain and hematomas, and a low incidence of complications. 21,22 Therefore the Closure procedure is rapidly gaining popularity. Since the procedure has the promise of improving the care of many of our patients, we wanted to review our initial experience. METHODS The Closure procedure consists of controlled collagen denaturization of an incompetent superficial vein to ablate the venous lumen diameter with radiofrequency-resistive heating of the vein wall. This is controlled with vein wall temperature and impedance feedback. A dedicated microprocessor-controlled bipolar generator and catheter with collapsible electrodes are introduced percutaneously into the vein lumen. High-resolution scanners (full-featured HDI 5000 with SonoCT option) handled by experienced registered

2 JOURNAL OF VASCULAR SURGERY Volume 40, Number 3 Hingorani et al 501 vascular technologists were used for all procedures. The GSV was punctured at the knee level under ultrasound guidance (linear 7-4 MHz probe inserted in a sterile cover with acoustic coupling gel) and a inch guide wire was followed proximally to the common femoral vein. The introducer sheath was inserted, and the radiofrequency catheter was placed over the wire to approximately 1 cm from the first tributary of the GSV under direct ultrasound visualization. Infiltration over the GSV with tumescence solution (300 ml of normal saline solution, 50 ml of 1% lidocaine with 1:100,000 epinephrine, 10 ml of sodium bicarbonate) under ultrasound guidance was performed to compress the GSV and protect the skin from thermal damage. Our technique for performing RFA of the GSV carefully followed all steps suggested by the manufacturer, and the initial 5 procedures were performed under direct observation of company representatives. Treatment temperature of 85 C was maintained during treatment while pulling back the catheter. Infusion with heparinized saline solution (5000 U in 500 ml of saline solution) through the catheter was maintained at a rate of 1 drop per second. The catheter was withdrawn at a rate of 1 cm/min for the first3cmof the vein length for better seal, and at 2 to 3 cm/min thereafter. Impedance was kept at more than 150 ohms for 6F catheters and greater than 100 ohms for 8F catheters. At the end a completion duplex scan was obtained to assess changes in the treated GSV and to document patency of the common femoral, proximal femoral, and deep femoral veins. Stab avulsion of prominent varicosities and subfascial endoscopic perforator ligation were then performed when indicated. After the procedure a woven elastic bandage (Ace) was applied to the leg and thigh, and left in place for 48 hours in all patients. No limitations were placed on mobilization, and patients were encouraged to walk as soon as possible. Follow-up duplex scans were obtained when the patients returned to the office (International Commission for Accreditation of Vascular Laboratories accredited laboratory). The venous duplex scanning protocol included insonation of infrainguinal veins, including infrapopliteal and calf muscle veins, to rule out deep venous thrombosis (DVT). Special attention was paid to scanning of the GSV (occlusion, size, presence of clot) and its tributaries (patency of the inferior epigastric vein), and the saphenofemoral junction, to ensure the absence of GSV thrombus extension. Seventy-three lower extremities were treated in 66 patients with GSV reflux between April 2003 and February All patients underwent preoperative venous duplex scanning of the lower extremities. In all patients in this series the GSV was located greater than 5 mm from the skin level, with reflux time greater than 500 ms and diameter greater than 5 mm. There were 48 (73%) female patients and 18 (27%) male patients, with ages ranging from 26 to 88 years (mean, years). The severity of venous insufficiency in all patients was classified with CEAP guidelines. Two patients (3%) had CEAP class 2 disease, 19 patients (26%) had class 3 disease, 28 patients (38%) had class 4 disease, 4 patients (6%) had class 5 disease, and 20 patients (27%) had class 6 disease. 23 Seven patients (10%) were taking aspirin preoperatively, 1 patient was receiving warfarin sodium (Coumadin) therapy, and 1 patient was taking clopidogrel bisulfate (Plavix). None of the patients in this series was known to have a hypercoagulable state. Preadmission coagulation workup was limited to prothrombin time, partial thromboplastin time, and platelet count, which were normal in all but 1 patient who had a low platelet count of 97,000/ mm 3. General anesthesia was administered in 32 (44%) patients, regional femoral block in 33 (45%) patients, and local anesthetics with sedation in the remaining 8 (11%) patients. GSV diameter determined the size of RFA catheter used. In veins smaller than 8 mm in diameter a 6F catheter was used (54 cases), and in veins 8 mm or larger in diameter an 8F catheter was used (19 cases). RESULTS Postoperative follow-up. All patients underwent follow-up venous duplex scanning 2 to 30 days (mean, 10 6 days) after the procedure. These duplex scans documented occlusion of the GSV in 70 (96%) patients; in the remaining 3 patients the GSV was not obliterated. One of these patients underwent a successful repeat RFA procedure, 1 patient opted for operative stripping of the GSV, and the remaining patient refused further treatment. All patients with successful GSV closure (96%) were satisfied with the procedure. Patients with combined RFA and varicose vein excision had minor discomfort at the surgical site. In 1 female patient a 5-mm long superficial skin abrasion developed, which healed shortly after the procedure. Postoperative DVT. DVT was found in 12 limbs (16%). Eleven of these patients had an extension of the occlusive clot filling the treated proximal GSV segment as a floating tail beyond the patent inferior epigastric vein into the common femoral vein (CFV). In the other patient acute occlusive clots developed in the calf muscle (gastrocnemius) veins in the treated limb. Eight patients were readmitted and received anticoagulation therapy. Four patients were given enoxaparin on an ambulatory basis. All 12 patients with DVT underwent at least 1 follow-up duplex examination 3 to 14 days after the initial diagnosis. None had clinical evidence of pulmonary embolism. Ten of 11 patients with a CFV thrombus demonstrated complete thrombus resolution after 5 to 14 days. The remaining patient with calf muscle DVT demonstrated no resolution of the thrombi after 2 weeks of anticoagulation therapy. Although we diagnosed acute free-floating thrombus in the CFV (Fig) in 11 patients, only 3 underwent placement of an inferior vena cava (IVC) filter. These were the first 3 patients in whom we diagnosed such DVT after RFA of the GSV. The fourth patient was offered an IVC filter,

3 502 Hingorani et al JOURNAL OF VASCULAR SURGERY September 2004 Free-floating common femoral vein thrombus. but refused it, and follow-up venous duplex scans revealed that the thrombus had completely resolved. In addition, all 3 patients in whom an IVC filter was inserted demonstrated complete resolution of the CFV thrombus. On the basis of this early experience we decided to initially follow a more conservative approach with anticoagulation alone. If repeat duplex scans after 1 week of anticoagulation therapy did not result in resolution of the thrombus or adherence to the vein wall an IVC filter was inserted (n 1). DVT and patient demographic data. There was no statistically significant difference in the incidence of postprocedure DVT between male patients (2 of 18) and female patients (10 of 48; P.5). Similarly, we did not find a statistically significant difference in age between patients in whom DVT developed (mean age, years) compared with those in whom DVT did not develop (63 14 years; P.4). DVT and preoperative indications. CEAP classification in patients with postoperative DVT (average, ) was not statistically different from that in patients with an uneventful postoperative course (average, ). DVT and type of anesthesia. Post-procedure DVT developed in 7 of 32 (22%) patients who received general anesthesia, compared with 5 of the remaining 41 (12%) patients who received regional or local anesthesia (P.3). DVT and catheter size. Of the 19 limbs treated with the 8F RFA catheter, GSV clot extension developed in 5 (26%), compared with 7 of 54 (13%) limbs treated with the 6F RFA catheter (P.3). DVT and simultaneous varicose vein incision. No difference was found between the occurrence of DVT in patients who underwent the combined procedure (RFA and varicose vein excision) compared with patients who underwent GSV RFA only (P.7). DVT and postoperative mobilization. All patients were ambulatory within the first 6 postoperative hours. DISCUSSION The concept of endoluminal treatment of insufficient superficial veins is not new. Indeed, 5 decades ago investigators reported the use of electrocoagulation to obliterate enlarged greater and lesser saphenous veins. 24 This approach was further modified by Watts 25 and O Reilly, 26 but was later abandoned because of a high incidence of nerve injury and third-degree burns of the skin.

4 JOURNAL OF VASCULAR SURGERY Volume 40, Number 3 Hingorani et al 503 The Closure procedure, introduced in 1999, is one of the most exciting advances in venous surgery, with the potential to revolutionize the field. Randomized data examining this procedure compared with traditional open stripping suggest that the Closure procedure is associated with less postoperative pain, improved quality of life, faster recovery, and significant cost savings as a result of fewer sick days. 21,22 Furthermore, some have suggested that patients undergoing the Closure procedure may possibly be less prone to neovascularization, because the saphenofemoral junction is left intact. 27,28 While any surgical procedure in patients with varicosities is associated with the risk for DVT, the frequency of DVT has been reported to be quite low (about 1%) in the largest reported series. 21,29 However, duplex scanning in these series was performed at various time points, sometimes with an unspecified percentage of patients actually followed up and with unspecified protocols for duplex scanning. 21,22,29,30 If the thrombus extension is temporary, duplex scanning at 1 to 2 weeks after the procedure may be too late to image thrombosis. Furthermore, most of these reports have been supported by the manufacturers. This has led to calls for rigorous, unbiased prospective trials. On the other hand, in 1 series not financially supported by manufacturers, DVT developed in 2 of 29 (7%) patients after the procedure. 31 In this series the catheter was placed via an incision in the groin and was passed down the vein. One patient had popliteal vein DVT, and the other patient had DVT of the treated extremity 6 weeks after the procedure. In addition, the FDA website ( medwatch/index.html) contains 24 reports of adverse outcomes associated with the Closure procedure, 4 of which include pulmonary embolism and 22 with DVT or ascending thrombosis. 32 These may raise the issue of the true incidence of DVT after closure, because it is suspected that this may represent gross underreporting. 33 These data suggest that further study of the early effects of the Closure procedure is necessary. As a possible solution to this issue, a group of investigators suggested the routine use of low molecular weight heparin (LMWH) as thrombosis prophylaxis, because this might prevent postoperative DVT. 34 This suggestion is intriguing, but not universally agreed on. One of the main criticisms of the published data is the limited follow-up in reports of the Closure registry. 35 Long-term results for closure of the GSV are unknown, because up to 2 years of follow-up with duplex scanning has been documented in only a subset of the entire registry. 36,37 It is hoped that this issue can be further addressed as more centers report their experience. The question still remains as to how permanent the Closure procedure is. 35 Data from the VNUS Closure Registry indicated that complete occlusion of the GSV is seen in 93% of limbs at 1 week, 86% of limbs at 6 months, 83% of limbs at 12 months, and 85% of limbs at 24 months. These results indicate that the percentage of durable saphenous vein occlusions appears to decrease over time and that further examination is needed. 29 While the goal of the Closure procedure is to denature the collagen in the wall of the vein in a bloodless field with no resultant thrombus, the actual result may not be so ideal. We suspect that the combination of thrombosis, resorption of thrombus, intimal damage, shrinkage, and denaturization of the vein wall all probably contribute to the final results of the Closure procedure. While thrombus in the middle of the GSV with the denatured vein above and below this area may still produce an adequate result, thrombus above or below the denatured vein and exposed to the venous circulation is also a possibility. Indeed, some DVT reported from the group supported by the manufacturer described thrombus extension into the CFV. One of these was a floating thrombus extending from the orifice of the GSV in a patient with multiple post-procedure pulmonary emboli. 30 Possible causes of postoperative thrombosis with propagation to the deep system in our patients include undiagnosed hypercoagulable states or local damage to the endothelium from the catheter or electrodes despite careful attempts to position the catheter and open electrodes in the proximal GSV under direct visualization with duplex ultrasound guidance. It is also possible that thrombus may form in the remaining GSV stump, 27 and may propagate into the CFV. If the vein went into spasm during the procedure as a result of placement of the guide wire or catheter, or was collapsed from the tumescence solution, it may appear to be sealed at the end of the procedure. Later, when the spasm reverses, the lumen may open and enable blood to enter an area with damaged endothelium, with resultant thrombus formation. Several factors could potentially explain the higher incidence of DVT in our patients. They were older and had more severe venous stasis, compared with patients in other series. 21,29 In these studies mean patient age was less than 50 years, compared with 62 years in our series. Most of our patients (75%) had CEAP class 4 disease, compared with class 2 disease in at least 75% of patients in the other studies. There is evidence in the literature that increased age is associated with hypercoagulability. 38,39 Although the Virchow triad correlates venous stasis with thrombus formation, to our knowledge there are no published articles that confirm the association of primary venous insufficiency with hypercoagulability. Notwithstanding the probable theories concerning the formation of thrombus with the Closure procedure, further careful examination is needed. Our experience suggests that early postoperative duplex scanning is essential, and should be mandatory in all patients undergoing RFA of the GSV. We thank Anne Ober for editorial assistance. REFERENCES 1. Callam MJ. Epidemiology of varicose veins. Br J Surg 1994;81: US Department of Health, Education and Welfare. Health statistics from the National Health Survey. Chronic conditions causing limitations of activities: United States July 1959-June Series B, No. 36.

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