Genicular Artery Embolization: A Promising Treatment Option for Recurrent Effusion Following Total Knee Arthroplasty

Abstract

Background:

Selective genicular artery embolization (GAE) has shown promise as a minimally invasive treatment option for persistent symptomatic recurrent effusions (REs) following total knee arthroplasty (TKA).

Purpose:

We sought to investigate the radiographic and clinical success of GAE for RE after TKA.

Methods:

We performed a retrospective review of prospectively collected data on primary and revision TKA patients with RE, both hemorrhagic and non-hemorrhagic, who underwent GAE between 2019 and 2021 with a minimum of 6-month follow-up. All embolization procedures were performed by a single interventional radiologist. Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores were collected prior to GAE and at 1, 3, and 6 months post-procedure. Recurrence of effusion following GAE was assessed at 6 months using ultrasound.

Results:

Seventeen patients, 10 female and 7 male, with 18 TKAs and a mean (SD) age of 63.1 (8.6) years were included. We saw a mean (SD) of 36.1 (24.4) and 3.3 (3.0) point improvement in WOMAC and VAS scores, respectively. In addition, 14 of the 18 TKAs (77.8%) seen at final follow-up had complete resolution of effusion confirmed by ultrasound.

Conclusion:

Our retrospective review found that a majority of patients showed significant clinical improvement and resolution of effusion following GAE. These findings suggest that GAE may be an effective minimally invasive treatment option for RE following TKA and should be further investigated.

Introduction

Recurrent effusion (RE) following total knee arthroplasty (TKA) can lead to significant patient discomfort and dissatisfaction. The incidence of general RE is not well reported, but that of recurrent hemorrhagic effusion ranges from 0.3% to 1.6% following TKA [16,17]. Recurrent effusion can ultimately lead to joint stiffness, decreased function, and even periprosthetic joint infection (PJI) [23]. While the overall incidence of symptomatic RE after TKA appears to be low, a proper understanding of the underlying pathology and treatment options is paramount.

Conservative management of RE, with cessation of anticoagulants, aspiration, rest, ice, elevation, and compressive dressings, has demonstrated success in many patients [16]. If conservative measures fail or long-term cessation of anticoagulation is not medically appropriate, open or arthroscopic synovectomy or even revision TKA can be considered [16].

Genicular artery embolization (GAE) has been well documented as a treatment option for recurrent hemorrhagic effusions [12]. Furthermore, selective GAE has shown promise for reducing pain and synovial proliferation associated with non-hemorrhagic effusions secondary to osteoarthritis and inflammatory arthritis. Intraarticular neovascularization and an increase in inflammatory cytokines lead to synovial hypertrophy, and subsequently, REs. Additionally, sensory nerves proliferate causing significant pain and discomfort [18]. Genicular artery embolization can be help to limit neovascularization and proliferation of sensory nerves within the knee synovium, and by extension limit the recurrence of effusions and pain [10,11]. During GAE, angiography is performed, allowing for identification of hypervascular synovium, vascular abnormality, or vascular damage [23]. Once the pathologic vasculature surrounding the knee joint is localized, selective embolization is initiated using coils or other microparticles [8].

There are multiple case series and case reports that demonstrate the success rate of GAE for recurrent hemorrhagic effusions following TKA [6,13,21,22]. However, to our knowledge, only one prior study has evaluated patient-reported outcomes following GAE [15]. In addition, we are not aware of any studies that report the efficacy or outcomes of GAE for recurrent non-hemorrhagic effusions following TKA. The purpose of this study was to investigate the success of GAE for patients suffering from RE, both hemorrhagic and non-hemorrhagic, after TKA, using ultrasound and clinical outcome scores.

Methods

After Institutional Review Board approval, a retrospective review of prospectively collected data was performed on 17 symptomatic patients (18 knees) that developed spontaneous RE following TKA between May 2019 and March 2021. As part of our interventional radiologist’s standard of care, all patients were followed with patient reported outcomes, including the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores prior to and following GAE. All TKAs were performed by a single fellowship trained adult reconstruction surgeon from 2009 to 2019 who performs an average of 500 primary TKAs and 50 revision TKAs per year (AO). Chart review revealed patient demographics and surgical details (Table 1). Patients were excluded if data was incomplete, including a lack of 6-month post GAE ultrasound. Additionally, patients were excluded if their RE was secondary to infection or mechanical complications requiring revision of their TKA. One patient was excluded for insufficient follow-up. Five patients were offered, but never underwent GAE; one patient moved, two patients declined treatment, one patient contracted COVID-19, and one patient decided to proceed with knee revision.

Table 1.

Demographics and primary outcomes.

Demographics	Outcomes
Mean age in years (SD)	63.1 (8.6)
Gender	10 women, 7 men
Body mass index (SD)	29.9 (4.2)
Laterality	7 right, 11 left
Primary TKA/revision TKA	12 primary, 6 revision
Hemorrhagic/non-hemorrhagic	5/13
Time to geniculate artery embolism in years (SD)	3.1 (2.8)
Successful treatment	14/18 (77.8%)

TKA total knee arthroplasty.

Seventeen patients (10 female, 7 male), with a mean age (standard deviation [SD]) of 63.1 (8.6) years, who had 18 TKAs were included in the analysis. From these patients we reviewed 12 primary and 6 revision TKAs. These included 14 posterior stabilized components, 2 cruciate retaining components, and 2 constrained condylar knee components. All patients, except for 2, received cemented components. The mean interval between TKA and GAE (SD) was 3.1 (2.8) years. Thirteen patients had non-hemorrhagic RE while 5 patients had hemorrhagic RE. At the time of effusion, 7 patients were on anticoagulants including: antiplatelet agents (N = 4), and warfarin (N = 2), and apixaban (N = 1). Anticoagulation was held prior to GAE based on the Society of Interventional Radiology guidelines [20]. Antiplatelet agents were not withheld before or after the procedure. Apixaban was held 24 hours prior to the surgery in all patients without chronic kidney disease (CKD). Patients with CKD did not take apixaban within 48 hours of the procedure. All apixaban was resumed 24 hours following the embolization. Warfarin was titrated to an INR of <1.8 and resumed the day of the embolization. No patients had a known coagulation disorder. Of note, no patient had a history of trauma at the time of bleeding.

RE was diagnosed by the presence of effusion on a clinical exam and then confirmed with aspiration. Pain with palpable effusion was the criteria used to determine if aspiration was warranted. In addition, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were included in each patient’s analysis. If a patient experienced constitutional symptoms of infection, had elevated inflammatory markers and/or had purulent fluid in the aspirate, the aspirate was then sent for fluid analysis. In these cases, negative cultures and synovial analysis were required to rule out periprosthetic joint infection prior to GAE. Aspirations with gross blood present were considered hemorrhagic, whereas those with straw-colored synovial fluid were considered non-hemorrhagic. In total, there were 5 hemorrhagic effusions and 13 non-hemorrhagic effusions.

Anteroposterior and lateral radiographs were reviewed by the operative surgeon prior to GAE for signs of component loosening, osteolysis, or mechanical failure. In patients with signs of implant loosening, GAE was not performed, and revision arthroplasty was pursued. Radiographs were interpreted using our institution’s viewing software (Sectra Workstation IDS7, Sectra, Linkoping, Sweden). Radiographs were reviewed systematically as described by Meneghini et al [14] in the Modern Knee Society Radiographic Evaluation System and Methodology for TKA.

All patients were treated with conservative treatment first including joint aspiration, compression, rest, ice application, and cessation of anticoagulation when possible. For RE that failed conservative treatment, interventional GAE was performed after discussion of treatment options with the patient.

All GAE procedures were performed by a single board-certified interventional radiologist (C.K.). Access was gained from either the ipsilateral or contralateral femoral artery using an anterograde or “up-and-over” technique, respectively. The vasculature was visualized using angiography. Once identified, the pathologic genicular artery was embolized using either 75 uM embozene (Boston Scientific) or 100 to 300 uM Embospheres (Merit Medical). Success of embolization was verified through angiography prior to conclusion of the procedure with near stasis within the target vessel as the technical endpoint. After embolization, no limitations were given regarding patients’ activity level or range of motion of the affected knee.

Successful treatment of RE with GAE was defined as lack of joint effusion visualized on ultrasound at 6 months post-procedure at the discretion of a board-certified radiologist. Additionally, a physical examination consistent with no joint effusion was required to consider the treatment successful. Complications after GAE were recorded. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) scores were collected at 1-, 3-, and 6-month follow-up after GAE [9].

Results

Angiography demonstrated genicular artery hypertrophy and synovial hypervascularity with “blush-type” appearance in all patients (Fig. 1). The detail of the specific arteries embolized are outlined in Table 2. No vascular malformations or pseudoaneurysms were identified. Spherical embolic particles ranged in size from 75 to 300 uM with eight patients receiving a 75-uM particle and the remaining receiving 100 to 300 uM particles. Pre- and post-embolization angiography images can be seen in Fig. 2.

Fig. 1.

Pre-embolization angiography of a TKA with RE. Angiography demonstrating early filling of tortuous genicular vessels (left). Late filling demonstrating hypertrophic vascularized synovium (right, red arrows).

Table 2.

Arteries embolized.

Patient	Aspiration quality	Successful GAE	Artery embolized
Patient 1	NH	No	IL
Patient 2	H	No	SM, SL, AT
Patient 3	NH	No	D, SL, AT
Patient 4	NH	Yes	SM, SL, AT
Patient 5	NH	Yes	D
Patient 6	NH	Yes	D, AT, SL
Patient 7	NH	Yes	D
Patient 8	H	Yes	SL, IL
Patient 9	NH	Yes	SL, SM, IL
Patient 10	H	Yes	D, SL, AT
Patient 11	NH	Yes	D, SL, IL
Patient 12	NH	No	SL, SM, D
Patient 13	H	Yes	D, SL, AT
Patient 14	NH	Yes	SM, SL, IL, AT
Patient 15	NH	Yes	D, SL
Patient 16	NH	Yes	SL, SM, IL
Patient 17	H	Yes	SM, SL
Patient 18	NH	Yes	D, SM, IM, SL

D descending geniculate, SL superior lateral geniculate, SM superior medial geniculate, IL inferior lateral geniculate, IM inferior medial geniculate, M middle geniculate, AT anterior tibial recurrent geniculate, H hemorrhagic effusion, NH non-hemorrhagic effusion, GAE geniculate artery embolization.

Fig. 2.

Pre- and post-embolization angiography. Completion angiography after superselective superior medial, superior lateral, anterior tibial recurrent, descending genicular, and inferior medial genicular artery embolization with delayed imaging demonstrating markedly decrease synovial vascularity.

Fourteen (77.8%) patients seen at final follow-up had success of GAE, defined as complete resolution of the RE confirmed by ultrasound. Of the 4 patients who failed GAE, 3 presented with non-hemorrhagic fluid, and 1 with hemorrhagic fluid. In addition, 1 patient underwent revision TKA with final resolution of RE symptoms. The mean ROM prior to GAE was 114.2º (14.9 SD). Following GAE, the mean ROM was 120.4º (8.4 SD), representing a mean 6.2º improvement in ROM.

Mean WOMAC scores for pre-embolization and 1, 3, and 6 months post-procedure were 73.9 (12.9 SD), 40.9 (16.8 SD), 38.4 (19.4 SD), and 37.8 (17.2 SD), respectively. Overall, we saw a mean of 36.1 (24.4 SD) point improvement in WOMAC scores (Fig. 3). In addition, mean VAS scores for pre-embolization and 1, 3, and 6 months post-procedure were 7.4 (1.8 SD), 4.5 (2.1 SD), 4.1 (2.0 SD), and 4.1 (2.1 SD), respectively. Overall, we saw a mean of 3.3 (3.0 SD) point reduction in VAS scores (Fig. 4).

Fig. 3.

WOMAC Score vs. Time. There was a mean reduction of WOMAC scores by 36.1 over the study period. The reported MCID for WOMAC improvement is 10.0.

Fig. 4.

VAS Score vs. Time. There was a mean reduction of VAS scores by 3.3 over the study period. The reported MCID for VAS improvement is 2.26.

Only 1 patient suffered from a minor skin complication following GAE, localized skin ischemia that resolved at 6-months post-procedure with observation, without cosmetic consequences (Fig. 5). The descending geniculate artery, superior lateral geniculate artery and the anterior tibial recurrent artery were embolized in this patient. Based on anatomic location, the anterior tibial recurrent artery was likely the embolized artery that led to skin ischemia.

Fig. 5.

Clinical photo of skin ischemia post-embolization. photo demonstrating localized skin ischemia experienced by one patient. Initial image (left), 3-month follow-up (middle), and 6-month follow-up (right). Completely resolved at 6 months with observation.

Discussion

While many prior case series and case reports exemplify the success of this procedure in treating recurrent hemorrhagic effusions [12,13,22], there is little information on the treatment of recurrent non-hemorrhagic effusions following TKA. Furthermore, there is a lack of information on patient reported outcomes following GAE. Our retrospective study suggests that GAE for RE following TKA may be successful in treating RE and improving patient reported outcomes.

Our study is not without limitations. First, our study is a retrospective review of prospectively collected data. Therefore, inherently some data may remain incomplete. In addition, patients treated with GAE and then subsequently lost to follow-up were not included. Regardless, we report a 77.8% success rate for our final endpoint of RE resolution on ultrasound at 6 months. Additionally, due to the low incidence of RE following TKA, we present a case series without a control group. Future research could include a control group with conservative treatment.

Prior studies evaluating initial GAE for recurrent hemorrhagic effusions have reported a success rate ranging from 50% to 100% [6,7,12,13,22]. For patients in which initial GAE was unsuccessful, repeat GAE was found to be effective [6,7,12,22]. Our study found that 77.8% of patients had complete resolution of RE, confirmed by ultrasound and lack of palpable effusion on exam, after initial GAE. Four patients failed GAE and repeat embolization was not attempted.

We found significant improvement in WOMAC scores following the procedure. Interestingly, we noted a sharp improvement in WOMAC scores within 1 month of the embolization. We saw little improvement occurring from 1, 3, and 6 months following the procedure. This indicates that embolization has early and effective results. Our study found an a mean 36.1 point improvement in WOMAC scores at final follow-up, which greatly surpasses the reported minimal clinically important difference (MCID) of 10 for the WOMAC score following TKA [4]. Only 1 study, by Ogilvie et al, reported on patient outcomes after GAE for RE after TKA. They found that the VAS score decreased from 9.5 to 1.25 following the GAE procedure [15]. Similarly, the current study had a 3.3 point mean reduction of VAS scores, further demonstrating the benefits of GAE. The reported MCID for VAS improvement is 2.26, further supporting the clinical improvement offered by GAE [5]. Brander et al found that on average, TKA patients had a postoperative VAS score of 1.6 at 1-year follow-up [3]. While a mean VAS score of 4.1 may represent a dissatisfied patient, it is well documented that nearly 19% of TKA patients are dissatisfied following TKA [2]. Furthermore, the current study targets a population including both primary and revision TKA patients that were already dissatisfied and thus required further treatment. Although not perfect, we found that GAE provides clinical improvement in pain following GAE for RE.

For TKA patients, the most dreaded complication after GAE for RE is PJI [12,13]. In a large systematic review of 91 patients with recurrent hemorrhagic effusions treated with GAE, Kolber et al [12] reported a 2% incidence of PJI. Minor complications after GAE include transient cutaneous ischemia and skin ulceration, with incidence ranging from 6% to 40% [1,12]. Inguinal hematoma from the embolization entry site is another rare complication reported in the literature [22]. Additionally, small bone infarctions have been reported in the GAE literature, but they have not been shown to have any effect on clinical outcomes [19]. Our study demonstrates a 5.6% (N = 1) incidence of minor complications. One patient experienced localized skin ischemia that healed without intervention at 6 months.

In conclusion, RE following TKA is a rare but a serious complication. Our retrospective study found that GAE produced a significant clinical improvement and resolution of effusion in most patients. We have found GAE to be a viable minimally invasive treatment for hemorrhagic and non-hemorrhagic RE following TKA and should be further investigated as a potentially promising treatment option for this difficult patient population.