Safety, procedural success and outcome of the Aspirex®S endovascular thrombectomy system in the treatment of iliofemoral deep vein thrombosis – data from the Arnsberg Aspirex registry
Abstract
Summary.Background: Percutaneous mechanical thrombectomy (PMT) represents a treatment option in addition to conventional therapy for patients with iliofemoral deep vein thrombosis (DVT). We sought to determine the safety, patency and short-term outcome of the Aspirex®S catheter as a rotational mechanical thrombectomy device in the endovascular treatment of iliofemoral DVT. Patients and methods: 56 patients (66 % female, median age 51 years) undergoing mechanical thrombectomy with the Aspirex®S catheter for endovascular treatment of iliofemoral DVT were included in the analysis. Device- and procedure-related complications, prevention of post-thrombotic syndrome (PTS) and patency rates were determined at baseline and at 1, 6 and 12 months after intervention. Results: No device-related complications or malfunction occurred. Procedure-related complications (rehospitalization, re-occlusion of target vein, prolonged hospitalization resulting from access site complication) were seen in 14 % of patients. PMT was followed by implantation of a dedicated venous stent in all patients. Low PTS reflected by a revised venous clinical severity score (rVCSS) of < 3 and a clinical, etiologic, anatomic and pathophysiologic (CEAP) score of < 3 were achieved in 64 % of the patients at 12 months. Patency was 95 % after 1 month, 94 % after 6 months and 87 % after 12 months. Conclusions: Even though long-term studies are missing, PMT of iliofemoral DVT using the Aspirex®S rotational thrombectomy device as a standalone approach exhibited an excellent patency at short term associated with substantial prevention of moderate to severe PTS and low device-related complications including bleeding.
Introduction
Deep vein thrombosis (DVT) and its complications results in the third most common cause of cardiovascular mortality after myocardial infarction and cerebral vascular disease. Recent European population studies reported a DVT incidence of 70–140 cases/100,000 person-years and a hospitalization of about 50,000 patients per year in Germany only [1–3]. Iliac veins are involved in about 40 % of iliofemoral thromboses [3], while standard treatment fails to achieve sufficient recanalization of these veins in about 70 % of cases [4]. Inadequate recanalization of venous blood flow causes a persistent outflow obstruction with hemodynamic effects, inducing valve incompetence of the deep veins and subsequent valve failure of the saphenous veins of the affected lower extremity. The resulting post-thrombotic syndrome (PTS) is a chronic debilitating clinical entity characterized by a spectrum of disease severity from chronic leg swelling and pain, to skin changes, claudication, and in severe cases ulceration [4]. The overall prevalence of PTS in Germany is reported to be about 5 % [5]. Moreover, the management of PTS is challenging, as to date, there is no effective treatment of established PTS and the effectiveness of most preventative measures is debated. Both signify its significant economic burden for public health [6, 7].
In only 20–30 % of iliac vein thrombosis a sufficient recanalization is observed with anticoagulation only. Catheter-based endovascular techniques have revolutionized therapeutic options for DVT by altering the risk-benefit ratio of intervention. Various methods now exist including catheter directed thrombolysis (CDT), pharmaco-mechanical CDT (PCDT), and percutaneous mechanical thrombectomy (PMT) [8–10]. The main complication of CDT is bleeding, of which the majority is confined to the venous access site. The PCDT concept may be used to reduce the bleeding risk by lowering the required dosage of thrombolytic agents. Even though so far not widely used, PMT as a standalone solution without the usage of a thrombolytic agent represents an attractive alternative offering improved luminal patency without relevant bleeding risk [11].
The Aspirex®S endovascular system (Straub Medical, Wangs, Switzerland) for mechanical thrombectomy consists of a rotating over-the-wire device designed for efficient and rapid removal of occluding material. The rotations produce a continuous vacuum inside the catheter, which leads to aspiration of the material into the catheter and transportation into the collecting bag. The Aspirex®S device is designed for the use in fresh thrombotic or thromboembolic material since its head itself does not rotate, in the meantime avoiding the risk for vessel trauma, and may therefore being used in acute and subacute DVT [12].
The current analysis was performed to assess safety, efficiency and patency of the Aspirex®S rotational thrombectomy in iliofemoral DVT during a 12-months follow-up in a single-arm, single center, non-randomized registry.
Patients and methods
Patient characteristics
A total of 56 patients with ascending and descending iliofemoral DVT were included. DVT was defined as acute thrombotic occlusion with an onset of pain < 14 days. Subacute DVT was defined with symptoms > 14 days. Detailed patients’ characteristics are given in Table I. Venous occlusion was diagnosed prior to treatment on duplex ultrasound scanning (DUS), computed tomography venography or magnetic resonance venography. Occlusion was considered acute in 40 patients (71 %), subacute in 13 patients (23 %) and acute-on-chronic in 3 patients (6 %). In 53 % of the patients, May-Thurner syndrome represented the underlying pathology, in 18 % the pathology remained undetermined. Cancer associated compression with consecutive thrombosis counted for 9 %. In 16 % of treated patients a post-thrombotic syndrome (post-thrombotic alterations of venous vessel wall) was already present (Table II).
The clinical severity of diseased limbs was classified using the revised venous clinical severity scoring (rVCSS) score and the clinical, etiologic, anatomic and pathophysiologic (CEAP) score according to the reporting standards of Society for Vascular Surgery (SVS) [13, 14]. Table II gives an overview about the clinical stages at baseline. Table III provides information about target vessel location.
This study was approved by the local ethics committee (2017-537-f-S).
Intervention
All procedures were performed according to the local standard of care and up to the manufacturer’s instructions. Access was achieved under local anesthesia, monitored conscious sedation and local anesthesia or general anesthesia at the investigator’s discretion. The ipsilateral femoral or popliteal vein served as the main access site and puncture was performed under ultrasound guidance. After venography, the lesion was traversed using a variety of guiding catheters and guidewires. The Aspirex®S catheter was then inserted into the occlusion over the guidewire. The rotating helix of the Aspirex system, which is used for rotational thrombectomy, employs the Archimedes principle. The helix rotates within a thin-walled catheter at a rate of 40,000 revolutions per minute, which causes suction. Local thrombi are thus aspirated at the tip of the catheter and removed. Depending on vessel size, 6-F, 8-F, or even 10-F systems are available for use. In our cohort, 10 French Aspirex catheters were used in 84 % of the cases, 8 French catheters in 16 % of the procedures (Table IV). Afterwards, a repeat venogram and intravascular ultrasound analysis was performed to ensure technical success and to exclude target lesion complications. For stent deployment, the lesion was further pre-prepared by dilatation using a high-pressure balloon to the nominal diameter of the stent along the entire length of the disease anatomical site. Only dedicated venous stents were deployed. The stents were post-dilated to ensure complete expansion of the stent. After stent deployment, another repeat venogram was performed to ensure patency, adequate adaptation to the wall and coverage of the entire lesion.
Anticoagulation
Periprocedural doses of unfractionated heparin ranged between 5,000 IE and 10,000 IE (Table IV). Post-procedure anticoagulation was started immediately following the completion of the procedure. Patients were initially given full-dose low-molecular weight heparin for at least 24 hours post-procedure and transitioned to vitamin K antagonists (5/56 patients) or novel-oral-anticoagulant (51/56 patients) for continuous therapy. Anticoagulation was continued based on national and international guidelines for conservative treatment of DVT.
Study endpoints and follow-up
Technical success, minor procedure-related adverse events (hematoma, puncture-site bleeding), serious adverse events (procedure-related rehospitalization, re-occlusion of target vein, prolonged hospitalization resulting from access site complication), device malfunction and device-related complaints were analyzed.
For follow-up, patients were evaluated clinically and by duplex ultrasound at 1 month (FU1), 6 months (FU 2), and 12 months (FU3). Severity of PTS was measured by the usage of the rVCSS and the CEAP score. Patency was defined as target lesion restenosis < 50 % in DUS.
Statistics
Continuous variables are presented as median and range. Categorical data is presented as absolute number and percentage. Statistics were descriptive. Patency rates were calculated using survival analysis with the Kaplan-Meier method using SPSS v. 22 (SPSS, IBM Corporation, Armonk, NY) [15].
Results
Follow-up rates were 54/56 patients after 1 month, 49/56 patients after 6 months and 39/56 patients after 12 months. Mean follow-up intervals were 30 ± 10 days (FU1), 180 ± 30 days (FU2) and 360 ± 60 days (FU3).
Safety and procedural results
The technical success rate was 100 %. No device-related complications or malfunction occurred. Treatment duration ranged around 27 to 238 minutes (Table IV). In 4 of the cases a 10 mg t-PA Bolus was injected into the profunda femoral vein (PFV) via a catheter to restore blood inflow, as navigation of the Aspirex catheter into the PFV from an ipsilateral approach is not possible (Table IV). Procedure-related severe complications (rehospitalization, re-occlusion of target vein, prolonged hospitalization due to av-fistula operation) were seen in 8 (14 %) patients. Minor adverse events occurred in 20 % (Table VI). No bleeding complications occurred. A mean of 1.9 dedicated venous stents were implanted per lesion (Table IV).
Patency
Combined patency rates measured by duplex ultrasound with a definition of < 50 % restenosis of target vessel were 95 % at FU1, 94 % at FU2 and 87 % at FU3, respectively (Table V).
Clinical outcome
At 12-months follow-up, PTS analysis could reveal low PTS symptoms reflected by a CEAP score < 3 and a rVCSS score < 3 in 64 % of the patients. Moderate PTS symptoms reflected by a CEAP score > 3 (maximal 4) and a rVCSS score > 3 (maximal 6) were seen in 36 %. No severe PTS (CEAP score > 4, rVCSS > 6) was observed (Table VI).
Discussion
VTE is responsible for > 250,000 hospital admissions per year and is a major cause of morbidity and mortality in the United States [16]. So far, there are excellent guideline recommendations on anticoagulation therapy in VTE. However, using anticoagulation therapy only, 25–50 % of DVT patients are on the risk to develop PTS. Proximal DVT involving the common femoral and/or iliac veins, referred to as iliofemoral DVT, represents a disease process with a worse prognosis and higher risk for poor clinical outcomes. The adjunctive use of percutaneous transluminal angioplasty and stents for chronic venous outflow obstructions has been shown to prevent the recurrence of thrombosis, reduce PTS, improve quality of life, and enable healing of venous ulcers by removing the underlying venous outflow obstruction [17, 18, 25, 26]. Nonetheless, to date, consensus guidelines for the endovascular treatment of acute DVT controversially discuss endovascular treatment options for iliofemoral DVT [19] because of inconclusive study results.
The CaVent (Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis) trial is a well conducted mulicentric randomized (CDT vs. standard anticoagulation therapy) and controlled study analyzing the safety and efficacy of CDT in 189 patients (age 18–75 years) with a first diagnosis of iliofemoral DVT. Endpoints of this study were the patency of the treated veins after 6 months and incidence of a PTS after 24 months. Mean duration of local lysis was 2.4 days. In the CDT arm, 90 patients showed a complete recanalization after therapy, 37 patients did improve with a partial but functionally good venous reflow. Only 10 patients did not functionally improve. Beside of the CDT an endovascular therapy (venous angioplasty with or without stent implantation) was performed in 39 of the patients. There was a significant decrease of PTS incidence after 24 months in the CDT arm in comparison to the standard therapy (41.1 % vs. 55.6 %, p = 0.047). Patency analysis of the iliofemoral veins at 6 months proved the efficacy of the CDT after follow up (65.9 % vs. 47.4 %, p = 0.012). About 22 % of the CDT arm patients were diagnosed with a minor/major bleeding complication underlying the potential risk of CDT therapy.
Recently published data from the randomized controlled ATTRACT study raised concerns about the benefit of interventional procedures compared to standard-of-care anticoagulation. The devices for PCDT used in ATTRACT included the AngioJet thrombectomy system, the Trellis-8 peripheral infusion system and catheter-directed rt-PA infusion via a multi-sidehole infusion catheter. In ATTRACT, PCDT failed to significantly decrease the occurrence of PTS when compared to its occurrence in anticoagulation alone. At 24-months follow-up, PCDT showed PTS in 46.7 % versus 48.2 % when receiving anticoagulation alone (p = 0.56), while the bleeding risk was significantly increased [20]. Compared to the later limitation, using Aspirex®S PMT as a one-step approach, the risk for bleeding complications was minimal in our cohort except minor puncture site hematoma. Additionally, Aspirex®S PMT turned out to be highly effective in the prevention of moderate to severe PTS and was superior compared to the anticoagulation-only group of ATTRACT. The restriction to include iliofemoral DVT lesions only as to our protocol may be seen as a possible explanation for that difference as ATTRACT grouped iliofemoral and femoropopliteal DVT together. When taking just moderate and severe PTS in iliofemoral DVTs into account, ATTRACT also showed rates of 18.4 % in the PCDT group versus 28.2 % in the anticoagulation-only group [20, 21]. However, those hints from ATTRACT were not sufficiently powered to reach statistical significance.
On the other hand, it has been shown that about one quarter of patients experience recurrent DVT within the first five years after index DVT when traditional systemic anticoagulant therapy is provided only [22]. This high rate of relapse may result from the lack of treatment of the underlying cause of DVT. In our cohort, in about 53 % of the patients a May-Thurner syndrome could be found to have caused index DVT. As to our institutional protocol all lesions were therefore additionally secured by stent implantation after application of Aspirex®S PMT and intravascular ultrasound analysis. Other than the investigators of the ATTRACT study, who also used a high percentage of arterial stents – a fact that may be judged as a relevant limitation – we only used dedicated venous stents in our cohort. As compared to the arterial system, venous vessel stenting needs stents with larger diameter and higher radial force to serve its anatomical needs and to overcome underlying external compression [23, 24]. There are currently eight dedicated venous stents on the market in Europe: the Sinus venous stent and the Sinus obliquus stent (both Optimed, Ettlingen, Germany), the Vici venous stent (Veniti, Inc., Fremont, CA, USA), the Zilver vena venous self-expanding stent (Cook Medical, Bloomington, IN), the Venovo venous stent system (Bard, Tempe, AZ), the Abre venous stent (Medtronic, Minneapolis, Minnesota, USA) and the recently introduced Blueflow venous stent (plusmedica, Duesseldorf, Germany) [25, 26].
Therefore, a much-differentiated interpretation of the results from ATTRACT is recommended when restricting treatment of DVT to non-interventional strategies only. Our first data on the application of the Aspirex®S PMT at least revealed promising results without relevant safety concerns in the interventional treatment of fresh iliofemoral DVT without adjunctive thrombolysis.
Limitations
Irrespective of a high follow-up rate, the main confounder is the limitation to short term results up to 12 months only. Long term trials as well as more prospective, controlled trials with PMT or PCDT are warranted to confirm our results and conclusion.
Conclusions
The usage of the Aspirex®S PMT in treatment of acute and subacute iliofemoral DVT turned out to be safe without any device-related complications or technical failure. Severe PTS could be prevented in all patients after 1 year of follow-up, moderate PTS in 64 %. The system provided an excellent primary patency rate with restenosis < 50 % in 87 % of the patients at 12-months follow-up. Therefore, the Aspirex®S rotational thrombectomy device is suited to serve as a standalone approach in the treatment of iliofemoral DVT, at least in combination with subsequent implantation of a dedicated venous stent for co-treatment of the underlying pathology. Further studies with much larger cohorts are necessary to confirm long-term efficacy and to establish stratification recommendations.
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