- Email: [email protected]
Efficacy of intra-arterial catheter-directed thrombolysis for popliteal and infrapopliteal acute limb ischemia
Efficacy of intra-arterial catheter-directed thrombolysis for popliteal and infrapopliteal acute limb ischemia Wei Shuai Lian, PhD,a Sushant Kumar Das, PhD,b Xiao Xiao Hu, MD,a Xiao Jun Zhang, MD,a Xiao Yun Xie, PhD,a and Mao Quan Li, PhD,a Shanghai and Sichuan, People’s Republic of China
ABSTRACT Objective: The purpose of this study was to examine the efficacy and safety of catheter-directed thrombolysis (CDT) for first-line treatment of popliteal and infrapopliteal acute limb ischemia. Methods: A total of 28 consecutive patients (30 limbs) who underwent CDT for treatment of popliteal and infrapopliteal acute limb ischemia of thromboembolic origin between March 2012 and December 2017 were enrolled in this study. Per the Society for Vascular Surgery, limbs were classified into three runoff score groups: <5, good; 5 to 10, compromised; and >10, poor. The primary end points were primary patency and limb salvage assessed by Kaplan-Meier survival analysis. Secondary end points were technical success and clinical success. The Society for Vascular Surgery-recommended scale for gauging changes in clinical status was used to assess clinical success. Safety of the procedure was evaluated on the basis of periprocedural complications according to the Society of Interventional Radiology classification system. Results: Technical success was achieved in 25 (83.33%) treated limbs. Improved clinical status (grade þ3/þ2) was achieved in 93.33% of limbs. Primary patency and limb salvage for the entire cohort were 76.67% and 90% at 6 months and 60.0% and 76.67% at 12 months, respectively. The patency rate at 6 months and 12 months was 91.67% and 83.33% for the good runoff group, 80% and 60% for the compromised runoff group, and 50% and 25% for the poor runoff group, respectively. The patency rate of the good runoff group was significantly higher compared with that of the poor runoff group (P ¼ .004). Major amputation rate and mortality rate were 16.67% and 7.14%, respectively, at 12 months. The reintervention rate was 3.57% at 6 months and 21.42% at 12 months. Conclusions: CDT is safe and effective for revascularization of smaller vessel acute arterial thromboembolism as a primary therapy. However, more studies with a larger sample are warranted. (J Vasc Surg 2019;-:1-8.) Keywords: Catheter-directed thrombolysis; Below the knee; Acute lower limb ischemia; Thromboembolism
Acute limb ischemia (ALI) is a lethal event that without prompt treatment can result in not only limb loss but also death. In approximately 85% of the cases, the major cause of ALI is arterial thrombosis.1 Limb viability is compromised in acute ischemia as there is not enough time for new blood vessel growth to compensate for the loss of perfusion. Furthermore, the systemic sequelae of ischemia have also been reported to be associated with high morbidity and mortality rates in ALI patients.2 Endovascular options for mechanical revascularization of below-knee thromboembolic occlusions are limited. Rheolytic thrombectomy (AngioJet; Boston Scientific, Marlborough, Mass) and aspiration thrombectomy have shown promising results; however, treatment of smaller From the Department of Interventional and Vascular Surgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghaia; and the Department of Interventional Radiology, Affiliated Hospital of North Sichuan Medical College,
vessels with these techniques poses risk of vessel spasm, dissection, vessel rupture, or plaque disruption and distal embolization.3-5 In contrast to these techniques, intraarterial catheter-directed thrombolysis (CDT) can be useful in dissolution of thromboembolic plaques in smaller (infrapopliteal) arteries without any risk of vessel rupture.6 CDT is also considered superior to open surgical management when the thromboembolic occlusion is in infrapopliteal arteries. Incomplete revascularization remains an issue with balloon embolectomy. Moreover, it has been reported to have considerable morbidity and rare serious complications.7,8 Owing to enzymatic dissolution, CDT allows more effective clot resolution, particularly within distal arterial beds that are often resistant to open thrombectomy.6 Therefore, the purpose of this study was to evaluate the efficacy and safety of CDT for first-line treatment of acute popliteal and infrapopliteal thromboembolic occlusions.
Sichuan.b Author conflict of interest: none. Correspondence: Mao Quan Li, PhD, Department of Interventional and Vascular Surgery, Shanghai Tenth People’s Hospital, Tongji University, 301 Yanchang Rd, Shanghai 200072, People’s Republic of China (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvs.2019.03.081
METHODS The study was conducted in compliance with the Declaration of Helsinki. Informed consent to receive the CDT therapy and to follow up for angiographic evaluation was waived. Study population. This study prospectively analyzed patients with acute thromboembolism of the popliteal and infrapopliteal arteries who had undergone CDT at 1
2
Journal of Vascular Surgery
Lian et al
---
our vascular and interventional surgery department between March 2012 and December 2017. Patients between the ages of 18 and 80 years with lesions in popliteal and infrapopliteal arteries who presented with symptoms for #14 days were included in this study. The exclusion criteria were as follows: patients for whom antiplatelet therapy, anticoagulants, or thrombolytic drugs were contraindicated; patients with a recent (<6 weeks) ischemic stroke or cerebral bleeding; patients with recent (<6 weeks) surgery, severe hypertension (diastolic blood pressure >110 mm Hg, systolic blood pressure >200 mm Hg), current malignant disease, history of life-threatening reaction to contrast medium, or uncorrected bleeding disorders (gastrointestinal ulcer, menorrhagia, or liver failure); women with childbearing potential not taking adequate contraceptives or currently breast feeding; and pregnant women. Initial limb evaluation. Baseline limb conditions, such as sensory and motor deficits, rest pain, skin discoloration, and tissue loss, were noted. Severity of each limb was determined using the Rutherford classification scale. The modified version of the Society for Vascular Surgery (SVS) runoff score and the pedal runoff score were calculated both before and after the procedure with the help of angiographic images to determine the magnitude of thrombosis and the patency of runoff in each limb.9,10 The modified SVS runoff score ranges from 0 to 19 and indicates the severity of the disease with increments in the runoff score. It was determined by evaluating patency and degree of stenosis or occlusion in the popliteal artery (maximum score of 9 þ 1) and the tibial vessels (maximum score of 9 each). SVS runoff scores were assigned to each limb as follows: vessel with <20% stenosis, 0; 21% to 49% stenosis, 1; 50% to 99% stenosis, 2; less than half of the vessel length occluded, 2.5; more than half the vessel length occluded, 3. The score for the popliteal artery was multiplied by 3 before adding all four vessel scores together. Per the SVS runoff score, limbs were divided into three groups: good, <5; compromised, 5 to 10; and poor, 10. The pedal runoff score was determined angiographically by analyzing the patency of the dorsalis pedis, posterior tibial, and peroneal collateral vessels in the foot. Each limb was assigned a pedal runoff score ranging from 0 to 3 by allocating 1 point for each patent pedal vessel.10 CDT procedure. Each patient, on admission, received an unfractionated heparin bolus of 50 IU/kg followed by continuous infusion of 1000 IU/h, which was titrated to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the control value. CDT procedures were performed under digital subtraction angiography guidance (Fig 1). The Seldinger technique was used under local anesthesia to access the contralateral femoral
2019
ARTICLE HIGHLIGHTS d
d
d
Type of Research: Single-center prospective observational study Key Findings: Catheter-directed thrombolysis for popliteal and infrapopliteal acute limb ischemia of 30 limbs of 28 patients resulted in primary patency and limb salvage of 60.0% and 76.67% at 12 months, respectively. Reintervention rate at 12 months was 21.42%. Patency decreased with worse runoff score. Take Home Message: Catheter-directed thrombolysis appears safe and effective for treatment of popliteal and infrapopliteal acute limb ischemia.
artery with a 5F vascular sheath. Access to the abdominal aorta was then gained with the help of a 0.035-inch J wire. Subsequently, the abdominal aorta was catheterized by a standard 5F pigtail catheter, and digital subtraction angiography (INFX-800V, Infinix-i Coreþ; Canon Medical Systems USA, Tustin, Calif) of the abdominal aorta and lower limb arteries was carried out to determine the location and extent of the lesion. At the discretion of the operator, the 5F sheath was replaced with a 40- to 55-cm 6F therapeutic sheath (Radifocus Introducer II; Terumo Corporation, Tokyo, Japan). A hydrophilic 0.035-inch guidewire (Radifocus Guidewire M; Terumo Corporation) was used to cross the culprit lesion to determine the possible outcome of thrombolytic therapy. Thrombolytic therapy was initiated once the guidewire traversal test result was positive by placing a multiple-side hole thrombolytic catheter (Uni*Fuse; AngioDynamics, Latham, NY) into the proximal part of the thrombus in such a way that a few proximal holes of the catheter aligned adjacent to the proximal end of the thrombus. Such placement of the catheter was practiced to ensure adequate lysis of the thrombus. After the sheath and catheter were secured with a skin suture, the patients were transferred to the inpatient unit. Per the standardized thrombolysis protocol, a bolus dose of 10 mg of recombinant tissue-type plasminogen activator (Actilyse; Boehringer Ingelheim, Ingelheim, Germany) in a saline solution (50 mL) was injected during 30 minutes, followed by continuous infusion of recombinant tissue-type plasminogen activator at a rate of 1.0 mg/h; 500 IU of unfractionated heparin was infused through the catheter every hour. During infusion, the fibrinogen level was monitored every 6 hours. Moreover, lysis was monitored with periodic angiography every 8 to 12 hours. The infusion was terminated at once if any adverse event was encountered. In the absence of any adverse event and fibrinogen levels of $1.5 g/L, infusion was continued either until the completion of treatment or maximum infusion time of 48 hours. In the case that fibrinogen levels decreased to <1.5 g/L, the rate of infusion was reduced to half. Patients were kept under
Journal of Vascular Surgery Volume
-,
Number
Lian et al
3
-
Fig 1. Angiographic images from left lower limb of a 78-year-old man who presented with acute severe ischemia. a, Occlusion of left popliteal artery as well as of tibioperoneal trunk. b, The thrombolysis catheter across the opened popliteal artery and tibioperoneal trunk. c, Complete revascularization of arteries after catheter-directed thrombolysis (CDT).
continuous surveillance to detect any eventual signs of hemorrhage, and hematocrit and hemoglobin counts were frequently monitored. Aspirin (100 mg/d), clopidogrel (75 mg/d), and a statin (atorvastatin, 20 mg/d) were prescribed to each patient on discharge. Study end points. The primary end points evaluated were primary patency and limb salvage. In patients who required bilateral thrombolysis, each limb was analyzed independently. Secondary end points were technical success, clinical success, target region revascularization, and periprocedural and postprocedural complications. Definitions and outcome measures. Acute lower limb ischemia was defined as the limb with ischemic symptoms of acute onset and duration of #14 days. The Rutherford classification was used to classify the clinical severity of ischemia (Table I).9 Primary patency and limb salvage were determined in concordance with the SVS guidelines.9 Additional endovascular procedures (balloon angioplasty) to obtain sufficient distal perfusion were recorded but not considered technical failure of the CDT procedure. The need for such additional procedures within the same hospital stay after thrombus dissolution with CDT was still defined as primary patency. Limb salvage was defined as freedom from major amputation and maintained functional autonomy (walking or
standing). Major amputation was defined as an amputation performed above the ankle. Target lesion reinterventions were classified as major (conversion to bypass, thrombectomy, thrombolysis, or major surgical procedure) or minor (new endovascular procedure without the need for thrombectomy or thrombolysis). Clinical success (improvement in clinical status) was assessed according to SVS guidelines as an improvement in Rutherford grade of at least one category (Table I) with objective evidence of hemodynamic change (0.1 increase in ankle-brachial index [ABI]).9 According to the guideline, marked improvement in clinical status (grade þ3) refers to limbs having no ischemic symptoms and any foot lesions completely healed; ABI essentially “normalized” (increased to >0.9) after intervention. Moderately improved (grade þ2) clinical status refers to limbs having no open foot lesions, still symptomatic but only with exercise, and improved by at least one category; ABI is not normalized but has increased by >0.1 after intervention. Minimally improved (grade þ1) clinical status refers to limbs having >0.1 increase in ABI but no categorical improvement or vice versa (ie, upward categorical shift without an increase in ABI of >0.1). The technical success was defined as residual target stenosis of <30% (by visual estimation) without flow-limiting target vessel dissection at completion
4
Journal of Vascular Surgery
Lian et al
---
2019
Table I. Clinical categories of acute limb ischemia (ALI) Findings Category I. Viable
Description/prognosis
Doppler signal
Sensory loss
Muscle weakness
Arterial
Venous
None
None
Audible
Audible
None
Inaudible
Audible
Mild, moderate
Inaudible
Audible
Profound, paralysis (rigor)
Inaudible
Inaudible
Not immediately threatened
II. Threatened a. Marginally
Salvageable if promptly treated
Minimal (toes) or none
b. Immediately
Salvageable with immediate revascularization
More than toes, associated with rest pain
Major tissue loss or permanent nerve damage inevitable
Profound, anesthetic
III. Irreversible
digital subtraction angiography after intervention.9 Complications were categorized according to the Society of Interventional Radiology classification system.11
Table II. Baseline characteristics and comorbidities of patients
Follow-up. Patients were followed up in the outpatient department at 30 days, 6 months, and 12 months. The condition of the treated limb was assessed on each visit with ABI and duplex ultrasound scanning combined with magnetic resonance angiography. Any complications including distal thromboembolism were noted during follow-up. Furthermore, the need for any additional procedure or conversion to open surgery was also recorded.
Age, years
Statistical analysis. All statistical analyses were performed with GraphPad Prism version 5.0 software (GraphPad Software Inc, San Diego, Calif). Continuous variables were reported as means 6 standard deviations, and categorical variables were shown as percentages. Primary patency and limb salvage were assessed by Kaplan-Meier survival methods. A value of P < .05 was considered significant for all statistical analyses.
RESULTS Baseline characteristics of patients. A total of 31 patients (33 limbs) with below-knee ALI underwent CDT during the study period. Six patients were lost to followup. On phone call inquiry, one was found to be deceased and two had major limb amputation at other hospitals. The remaining three could not be contacted. Finally, a total of 28 patients (30 limbs) were available for reporting after intervention. Demographic data and comorbidities of all the patients are outlined in Table II. Baseline lesion characteristics. Baseline lesion characteristics are summarized in Table III. There were four cases (13.33%) of Rutherford grade I, 15 (50.0%) cases of Rutherford grade IIa, and 11 (36.67%) cases of Rutherford grade IIb. With regard to etiology of ischemia, nine limbs had embolic etiology as suggested by abrupt severe symptoms with history of either arterial fibrillation or coronary artery disease and a relatively healthy arterial
Study group
Male/female Arterial hypertension
Patients (N ¼ 28) 65.13 6 10.0 (41-78) 19/9 (67.85/32.14) 19 (67.85)
Coronary artery disease
7 (33.33)
ESRD (Cr >150 mmol/L)
2 (7.14)
Diabetes
15 (53.57)
Smoking history
19 (67.85)
COPD HTN
4 (14.28) 19 (67.85)
CAD
11 (39.28)
Atrial fibrillation
11 (39.28)
Multiple comorbidities
6 (21.42)
CAD, Coronary artery disease; COPD, chronic obstructive pulmonary disease; Cr, creatinine; ESRD, end-stage renal disease; HTN, hypertension. Categorical variables are presented as number (%). Continuous variables are presented as mean 6 standard deviation (range).
tree without collateral formation on imaging analysis. Seventeen limbs had in situ thrombosis and four had thrombosed popliteal artery aneurysm. Five patients had a pedal runoff score of 0; 11, score of 1; 9, score of 2; and 5, score of 3. In this study, 12 limbs had good (<5), 10 limbs had compromised (5-10), and 8 limbs had poor (>10) runoff scores. Immediate outcomes. Technical success was achieved in 25 (83.33%) treated limbs. In the remaining patients not characterized as having technical success (n ¼ 5), aspiration with a syringe through a standard angiographic catheter was successful (n ¼ 2) and surgical revascularization was successful (n ¼ 2). Early amputation was needed in one limb after unsuccessful thrombolysis. Early termination of CDT due to any adverse event was not encountered in any patients. Additional endovascular procedures (angioplasty) were performed in 18 limbs (78.26%) on the completion of thrombolysis to obtain sufficient distal perfusion. The acute failure rates (failure
Journal of Vascular Surgery Volume
-,
Number
Lian et al
5
-
Table III. Baseline lesion characteristics Characteristics Duration of symptoms at presentation, days
Limbs 6.5 6 2.1 (3-14)
Severity (Rutherford grade)
Table IV. Catheter-directed thrombolysis (CDT)-related and overall 30-day complications CDT-related 30-day complications Minor (SIR A, B: nominal or no therapy, no consequence)
3 1
I (viable limb)
4 (13.33)
IIa (marginally threatened limb)
15 (50.0)
Major (SIR C, D, E: requires therapy or permanent sequelae)
IIb (immediately threatened limb)
11 (36.67)
Majorddeath (SIR F: death)
III (irreversible)
0
Etiology In situ thrombosis Thrombosed popliteal aneurysm Embolization
17 (56.67) 4 (13.33) 9 (30)
Previous ipsilateral revascularization Femoropopliteal (PTA/stent) Femoropopliteal bypass
3 0
0
All 30-day complications Minor (SIR A, B: nominal or no therapy, no consequence)
3
Major (SIR C, D, E: requires therapy or permanent sequelae)
2
Majorddeath (SIR F: death)
1
Majordamputation (SIR E: major amputation)
1
SIR, Society of Interventional Radiology.
Ischemic signs and symptoms Claudication
19
Pain at rest
11
Cold and mottled skin
14
Cool and cyanotic
16
Sensory deficit
19
Motor deficit Ischemic ulcer or gangrene
7 0
SVS runoff score Good (<5)
12 (40)
Compromised (5-10)
10 (33.33)
Poor (>10)
8 (26.67)
Pedal runoff 3
5 (16.67)
2
9 (30.0)
1
11 (36.67)
0
5 (16.67)
PTA, Percutaneous transluminal angioplasty; SVS, Society for Vascular Surgery. Categorical variables are presented as number (%). Continuous variables are presented as mean 6 standard deviation (range).
to traverse an occlusion or occlusion within 30 days) were 6.67% (2/30) of limbs, all of which had a poor runoff score before intervention. Clinical success was assessed according to the SVS guidelines-recommended scale for gauging changes in clinical status. Markedly improved clinical status (grade þ3) was achieved in 50.0% of limbs (n ¼ 15); moderately improved (grade þ2), in 43.33% of limbs (n ¼ 13); and minimally improved (grade þ1), in 6.66% of limbs (n ¼ 2). All the patients with minimally improved clinical status had a poor runoff score before intervention. Complications. All CDT-related and overall 30-day complications are listed in Table IV. The early (30-day) outcomes indicate that overall, 96.42% (n ¼ 27) of
patients were alive. One limb required early amputation (3.5%) after unsuccessful thrombolysis, as outlined before. The primary CDT group had four 30-day complications. There was one major complication of a significant retroperitoneal/groin hematoma; surgical decompression was performed with a successful clinical outcome. Three minor complications, all of which were postprocedural groin hematoma, were recorded. All the patients with groin hematoma received analgesia and were monitored in the inpatient department. These patients were not discharged until the hematoma subsided. There was one death and one major amputation reported at 30-day follow-up. Long-term outcomes. Primary patency for the entire cohort at 6 months and 12 months was 76.67% and 60.0%, respectively (Fig 2). Limb salvage was 90% at 6 months and 76.67% at 12 months (Fig 3). The patency rate at 6 months and 12 months was 91.67% and 83.33% for the good runoff group, 80% and 60% for the compromised runoff group, and 50% and 25% for the poor runoff group, respectively (Fig 4). The patency rate of the good runoff group was significantly higher compared with that of the poor runoff group (P ¼ .004). However, the compromised and poor runoff groups did not have significant difference in the patency rate (P ¼ .146) in this study (Fig 4). Freedom from recurrent symptoms (restenosis or occlusion) was 83.33%, 40.0%, and 25.0% at 12 months for the runoff score category good, compromised, and poor, respectively. The absolute numbers of restenosis (50.0%) and occlusion (25.0%) were higher in the poor runoff group. Major amputation rate was 37.50% and 20.0% at 12 months for the poor and compromised runoff groups, respectively. With regard to the etiology of lesions, embolic ALI had slightly better outcome with 66.67% (8/12) patent limbs compared with thrombosed ALI with 55.55% (10/18) patent limbs at 12 months. However, the difference was not statistically significant (P > .05).
6
Lian et al
Journal of Vascular Surgery ---
2019
Fig 2. Kaplan-Meier estimates of primary patency for the entire cohort at 12 months. Fig 4. Kaplan-Meier estimates of primary patency in each of the runoff score groups at 12 months. There was a significant difference in primary patency between the good runoff score group (green line) and the poor runoff score group (red line; P ¼ .004). However, there was no significant statistical difference in primary patency of the compromised runoff score group (blue line) compared with either the good runoff score group (green line) or the poor runoff score group (red line).
Fig 3. Kaplan-Meier estimates of limb salvage for the entire cohort at 12 months.
A total of two major amputations (6.67%) and one death (3.57%) were recorded during the 6-month follow-up period. A total of five major amputations (16.67%) and two deaths (7.14%) were recorded at 12 months of follow-up. The reintervention rate at 6 months and 12 months was 3.57% (one patient) and 21.42% (six patients), respectively.
DISCUSSION Despite the need of multiple procedures, interval care in a higher level nursing care unit, and risk of hemorrhage, CDT is one of the most commonly used and well-established techniques for ALI.12,13 More recently, several other endovascular techniques, like rotational thrombectomy and aspiration thrombectomy, as well as open techniques, like balloon embolectomy, have been reported either alone or in combination with CDT to achieve a higher technical success rate and longer patency rate. However, either the study group has a small subset of patients with popliteal and infrapopliteal lesions or the study did not report the efficacy for infrapopliteal lesions.3,4,14,15 Exact status of the CDT procedure specifically for popliteal and infrapopliteal thromboocclusive lesions has not been documented.16-20 Rheolytic thrombectomy (AngioJet) has been reported to be successful in approximately half of cases as a stand-
alone technique. Moreover, it has been found to be only marginally effective in clearing more organized thrombus.3 In a previous study that used rheolytic thrombectomy to treat below-knee thromboembolism, it was found that 43% of the cases required stent to achieve technical success. Moreover, the revascularizations were complicated by further distal embolization in 10%.4 Although rheolytic thrombectomy achieved 70% successful revascularization for thromboembolism in a study by Ansel et al,5 that study had only a small subset of patients who presented with primary occlusions distal to the popliteal artery. In addition, almost half required post-thrombectomy thrombolytic infusion. Aspiration thrombectomy may also be attempted as a standalone technique. However, suction thrombectomy requires the delivery of large-bore catheters to the level of the thrombus in small lower extremity arteries with concomitant risks of spasm, dissection, vessel rupture, and plaque disruption.3 In this study, we established the efficacy of CDT therapy for popliteal and infrapopliteal thrombo-occlusive lesions. The study demonstrated that CDT can be performed with robust technical success for acute popliteal and infrapopliteal vessel thromboembolism. Technical success was achieved in 83.33% of the patients in this study. Patency rate and limb salvage at 12 months were 60.0% and 76.67%, respectively. Furthermore, in this study, we used a modified Rutherford scoring system that incorporated both the distal popliteal and individual runoff scores. This allowed us to quantify the contribution of both the popliteal artery and the tibial vessels to measure procedural success. The patency
Journal of Vascular Surgery Volume
-,
Number
Lian et al
7
-
rate was found to be incrementally curtailed by worsening runoff, with significant decreases as runoff category deteriorated. This finding is in accordance with Davies et al.21 In addition, with regard to safety, the study reconfirmed that CDT can be performed relatively safely from the perspective of complications. In smaller vessels, treatment of thromboembolic occlusion is challenging and can be associated with considerable morbidity and mortality if they are not adequately addressed. Passage of large-bore catheters to carry out these endovascular procedures in small vessels increases the risks of spasm, dissection, vessel rupture, and plaque disruption. Furthermore, most of these procedures are complicated by angiographically evident distal thromboembolic complications despite the use of distal protection.3 Distal embolism was also a concern in this study. Most patients displayed signs of perfusion deterioration, sometimes accompanied by severe pain requiring opiates, during thrombolysis. However, the symptoms were relieved with ongoing thrombolysis. This phenomenon might be due to dislodging of thrombus and possible embolism, but no severe complications secondary to it were reported. We believe the CDT technique adopted in this study might be the reason for this.20 Infusing the thrombolytic agent through the entire length of the thrombus may cause uncontrolled distal thrombus disruption and possible distal embolism. Instead, the technique adopted in this study, whereby thrombolytic agent is not infused through the entire thrombus but only to the proximal portion of the thrombus, protects against possible distal embolism. In this technique, the thrombus dissolves gradually at the proximal part and collateral flow through the previously occluded side branches occurs, whereas the distal portion of thrombus provides natural embolic protection distally. Therefore, these small emboli tend to migrate to these side branches. Thus, this study demonstrated that CDT can reach small vessels and can cause enzymatic dissolution of the thromboembolism without any substantial risk of distal or proximal embolism, vessel injuries, or dissection. In contrast to CDT, open surgical thrombectomy of small vessels is associated with higher risk and difficulties. Surgical thrombectomy of the tibial vessels often requires selective over-the-wire passage of Fogarty catheters into the affected vessel, which can be cumbersome through open approaches. If it is done from the common femoral artery with use of smaller diameter balloon catheters, the diameter of the larger superior femoral artery may lead to loss of the thrombus during retrieval despite proximal vessel clamping and cessation of antegrade flow. Distal approaches through pedal artery cutdown are also effective but require closure of the smaller dorsalis pedis or posterior tibial arteries, risking postsurgical vessel stenosis. In addition, open thrombectomy is considerably more invasive and is typically associated
with a much more substantial perioperative recovery than is typically seen after percutaneous revascularization.3 Therefore, the importance of CDT stands out for thromboembolism involving smaller vessels, and our study has reconfirmed it by achieving better technical and longer patency rates with no serious complications. Admittedly, several limitations to the study may exist. The study was a single-arm trial with no control group. The number of patients included in the study is small, and therefore the power to detect differences in outcome may be insufficient. Thrombolysis in the study was carried out using a single-dose strategy and cannot be compared directly with other thrombolytic studies using different thrombolytic strategies.
CONCLUSIONS CDT provides excellent treatment results with an acceptable complication rate in treatment of popliteal and infrapopliteal artery thromboembolic lesions. Thus, CDT might be considered in the treatment of smaller vessel ALI if adequate periprocedural care and 24/7 inpatient unit services are provided. We thank Morgan A. McClure, a medical editor at North Sichuan Medical College, for English grammar correction and revision.
AUTHOR CONTRIBUTIONS Conception and design: WL, SD, XX, ML Analysis and interpretation: WL, SD, XX, ML Data collection: WL, SD, XH, XZ Writing the article: SD Critical revision of the article: WL, XH, XZ, XX, ML Final approval of the article: WL, SD, XH, XZ, XX, ML Statistical analysis: SD Obtained funding: Not applicable Overall responsibility: ML WL and SD contributed equally to this article and share co-first authorship.
REFERENCES 1. Walker TG. Acute limb ischemia. Tech Vasc Interv Radiol 2009;12:117-29. 2. Theodoridis PG, Davos CH, Dodos I, Iatrou N, Potouridis A, Pappas GM, et al. Thrombolysis in acute lower limb ischemia: review of the current literature. Ann Vasc Surg 2018;52:255-62. 3. Landau D, Moomey C, Fiorella D. First-in-man experience with the ReVive PV peripheral thrombectomy device for the revascularization of below-the knee embolic occlusions. J Endovasc Ther 2014;21:747-54. 4. Spiliopoulos S, Katsanos K, Fragkos G, Karnabatidis D, Siablis D. Treatment of infrainguinal thromboembolic complications during peripheral endovascular procedures with AngioJet rheolytic thrombectomy, intraoperative thrombolysis, and selective stenting. J Vasc Surg 2012;56: 1308-16.
8
Journal of Vascular Surgery
Lian et al
---
5. Ansel GM, George BS, Botti CF, McNamara TO, Jenkins JS, Ramee SR, et al. Rheolytic thrombectomy in the management of limb ischemia: 30-day results from a multicenter registry. J Endovasc Ther 2002;9:395-402. 6. Working Party on Thrombolysis in the Management of Limb Ischemia. Thrombolysis in the management of lower limb peripheral arterial occlusionda consensus document. J Vasc Interv Radiol 2003;14:S337-49. 7. Norgen L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45:S5-67. 8. Pereira CE, Albers M, Romiti M, Brochado-Neto FC, Pereira CA. Meta- analysis of femoropopliteal bypass grafts for lower extremity arterial insufficiency. J Vasc Surg 2006;44:510-7. 9. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517-38. 10. Byrne RM, Taha AG, Avgerinos E, Marone LK, Makaroun MS, Chaer RA, et al. Contemporary outcomes of endovascular interventions for acute limb ischemia. J Vasc Surg 2014;59:988-95. 11. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003;14:S199-202. 12. Ouriel K, Shortell CK, DeWeese JA, Green RM, Francis CW, Azodo MV, et al. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 1994;19:1021-30. 13. Berridge DC, Kessel DO, Robertson I. Surgery versus thrombolysis for initial management of acute limb ischaemia. Cochrane Database Syst Rev 2013;6:CD002784. 14. Shammas NW, Dippel EJ, Shammas G, Gayton L, Coiner D, Jerin M. Dethrombosis of the lower extremity arteries using
15.
16.
17.
18.
19.
20.
21.
2019
the power-pulse spray technique in patients with recent onset thrombotic occlusions: results of the DETHROMBOSIS Registry. J Endovasc Ther 2008;15:570-9. Saxon RR, Teigen C. Novel thrombectomy system for below-the-knee and visceral arterial interventions: PRISM retrospective interim results. J Vasc Interv Radiol 2015;26: 149-50. Grip O, Kuoppala M, Acosta S, Wanhainen A, Åkeson J, Björck M. Outcome and complications after intraarterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion. Br J Surg 2014;101: 1105-12. Schrijver A, de Vries JP, van den Heuvel DA, Moll FL. Longterm outcomes of catheter-directed thrombolysis for acute lower extremity occlusions of native arteries and prosthetic bypass grafts. Ann Vasc Surg 2016;31:134-42. ski S. Safety Falkowski A, Poncyljusz W, Samad RA, Mokrzyn and efficacy of ultra-high-dose, short-term thrombolysis with rt-PA for acute lower limb ischemia. Eur J Vasc Endovasc Surg 2013;46:118-23. Pascoe H, Robertson D. Catheter directed thrombolysis for acute lower limb ischaemia: an audit. Australas Med J 2014;7:471-5. Lukasiewicz A, Lichota W, Thews M. Outcomes of accelerated catheter-directed thrombolysis in patients with acute arterial thrombosis. Vasc Med 2016;21:453-8. Davies MG, Saad WE, Peden EK, Mohiuddin IT, Naoum JJ, Lumsden AB. Impact of runoff on superficial femoral artery endoluminal interventions for rest pain and tissue loss. J Vasc Surg 2008;48:619-25.
Submitted Nov 6, 2018; accepted Mar 19, 2019.
ABSTRACT Objective: The purpose of this study was to examine the efficacy and safety of catheter-directed thrombolysis (CDT) for first-line treatment of popliteal and infrapopliteal acute limb ischemia. Methods: A total of 28 consecutive patients (30 limbs) who underwent CDT for treatment of popliteal and infrapopliteal acute limb ischemia of thromboembolic origin between March 2012 and December 2017 were enrolled in this study. Per the Society for Vascular Surgery, limbs were classified into three runoff score groups: <5, good; 5 to 10, compromised; and >10, poor. The primary end points were primary patency and limb salvage assessed by Kaplan-Meier survival analysis. Secondary end points were technical success and clinical success. The Society for Vascular Surgery-recommended scale for gauging changes in clinical status was used to assess clinical success. Safety of the procedure was evaluated on the basis of periprocedural complications according to the Society of Interventional Radiology classification system. Results: Technical success was achieved in 25 (83.33%) treated limbs. Improved clinical status (grade þ3/þ2) was achieved in 93.33% of limbs. Primary patency and limb salvage for the entire cohort were 76.67% and 90% at 6 months and 60.0% and 76.67% at 12 months, respectively. The patency rate at 6 months and 12 months was 91.67% and 83.33% for the good runoff group, 80% and 60% for the compromised runoff group, and 50% and 25% for the poor runoff group, respectively. The patency rate of the good runoff group was significantly higher compared with that of the poor runoff group (P ¼ .004). Major amputation rate and mortality rate were 16.67% and 7.14%, respectively, at 12 months. The reintervention rate was 3.57% at 6 months and 21.42% at 12 months. Conclusions: CDT is safe and effective for revascularization of smaller vessel acute arterial thromboembolism as a primary therapy. However, more studies with a larger sample are warranted. (J Vasc Surg 2019;-:1-8.) Keywords: Catheter-directed thrombolysis; Below the knee; Acute lower limb ischemia; Thromboembolism
Acute limb ischemia (ALI) is a lethal event that without prompt treatment can result in not only limb loss but also death. In approximately 85% of the cases, the major cause of ALI is arterial thrombosis.1 Limb viability is compromised in acute ischemia as there is not enough time for new blood vessel growth to compensate for the loss of perfusion. Furthermore, the systemic sequelae of ischemia have also been reported to be associated with high morbidity and mortality rates in ALI patients.2 Endovascular options for mechanical revascularization of below-knee thromboembolic occlusions are limited. Rheolytic thrombectomy (AngioJet; Boston Scientific, Marlborough, Mass) and aspiration thrombectomy have shown promising results; however, treatment of smaller From the Department of Interventional and Vascular Surgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghaia; and the Department of Interventional Radiology, Affiliated Hospital of North Sichuan Medical College,
vessels with these techniques poses risk of vessel spasm, dissection, vessel rupture, or plaque disruption and distal embolization.3-5 In contrast to these techniques, intraarterial catheter-directed thrombolysis (CDT) can be useful in dissolution of thromboembolic plaques in smaller (infrapopliteal) arteries without any risk of vessel rupture.6 CDT is also considered superior to open surgical management when the thromboembolic occlusion is in infrapopliteal arteries. Incomplete revascularization remains an issue with balloon embolectomy. Moreover, it has been reported to have considerable morbidity and rare serious complications.7,8 Owing to enzymatic dissolution, CDT allows more effective clot resolution, particularly within distal arterial beds that are often resistant to open thrombectomy.6 Therefore, the purpose of this study was to evaluate the efficacy and safety of CDT for first-line treatment of acute popliteal and infrapopliteal thromboembolic occlusions.
Sichuan.b Author conflict of interest: none. Correspondence: Mao Quan Li, PhD, Department of Interventional and Vascular Surgery, Shanghai Tenth People’s Hospital, Tongji University, 301 Yanchang Rd, Shanghai 200072, People’s Republic of China (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvs.2019.03.081
METHODS The study was conducted in compliance with the Declaration of Helsinki. Informed consent to receive the CDT therapy and to follow up for angiographic evaluation was waived. Study population. This study prospectively analyzed patients with acute thromboembolism of the popliteal and infrapopliteal arteries who had undergone CDT at 1
2
Journal of Vascular Surgery
Lian et al
---
our vascular and interventional surgery department between March 2012 and December 2017. Patients between the ages of 18 and 80 years with lesions in popliteal and infrapopliteal arteries who presented with symptoms for #14 days were included in this study. The exclusion criteria were as follows: patients for whom antiplatelet therapy, anticoagulants, or thrombolytic drugs were contraindicated; patients with a recent (<6 weeks) ischemic stroke or cerebral bleeding; patients with recent (<6 weeks) surgery, severe hypertension (diastolic blood pressure >110 mm Hg, systolic blood pressure >200 mm Hg), current malignant disease, history of life-threatening reaction to contrast medium, or uncorrected bleeding disorders (gastrointestinal ulcer, menorrhagia, or liver failure); women with childbearing potential not taking adequate contraceptives or currently breast feeding; and pregnant women. Initial limb evaluation. Baseline limb conditions, such as sensory and motor deficits, rest pain, skin discoloration, and tissue loss, were noted. Severity of each limb was determined using the Rutherford classification scale. The modified version of the Society for Vascular Surgery (SVS) runoff score and the pedal runoff score were calculated both before and after the procedure with the help of angiographic images to determine the magnitude of thrombosis and the patency of runoff in each limb.9,10 The modified SVS runoff score ranges from 0 to 19 and indicates the severity of the disease with increments in the runoff score. It was determined by evaluating patency and degree of stenosis or occlusion in the popliteal artery (maximum score of 9 þ 1) and the tibial vessels (maximum score of 9 each). SVS runoff scores were assigned to each limb as follows: vessel with <20% stenosis, 0; 21% to 49% stenosis, 1; 50% to 99% stenosis, 2; less than half of the vessel length occluded, 2.5; more than half the vessel length occluded, 3. The score for the popliteal artery was multiplied by 3 before adding all four vessel scores together. Per the SVS runoff score, limbs were divided into three groups: good, <5; compromised, 5 to 10; and poor, 10. The pedal runoff score was determined angiographically by analyzing the patency of the dorsalis pedis, posterior tibial, and peroneal collateral vessels in the foot. Each limb was assigned a pedal runoff score ranging from 0 to 3 by allocating 1 point for each patent pedal vessel.10 CDT procedure. Each patient, on admission, received an unfractionated heparin bolus of 50 IU/kg followed by continuous infusion of 1000 IU/h, which was titrated to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the control value. CDT procedures were performed under digital subtraction angiography guidance (Fig 1). The Seldinger technique was used under local anesthesia to access the contralateral femoral
2019
ARTICLE HIGHLIGHTS d
d
d
Type of Research: Single-center prospective observational study Key Findings: Catheter-directed thrombolysis for popliteal and infrapopliteal acute limb ischemia of 30 limbs of 28 patients resulted in primary patency and limb salvage of 60.0% and 76.67% at 12 months, respectively. Reintervention rate at 12 months was 21.42%. Patency decreased with worse runoff score. Take Home Message: Catheter-directed thrombolysis appears safe and effective for treatment of popliteal and infrapopliteal acute limb ischemia.
artery with a 5F vascular sheath. Access to the abdominal aorta was then gained with the help of a 0.035-inch J wire. Subsequently, the abdominal aorta was catheterized by a standard 5F pigtail catheter, and digital subtraction angiography (INFX-800V, Infinix-i Coreþ; Canon Medical Systems USA, Tustin, Calif) of the abdominal aorta and lower limb arteries was carried out to determine the location and extent of the lesion. At the discretion of the operator, the 5F sheath was replaced with a 40- to 55-cm 6F therapeutic sheath (Radifocus Introducer II; Terumo Corporation, Tokyo, Japan). A hydrophilic 0.035-inch guidewire (Radifocus Guidewire M; Terumo Corporation) was used to cross the culprit lesion to determine the possible outcome of thrombolytic therapy. Thrombolytic therapy was initiated once the guidewire traversal test result was positive by placing a multiple-side hole thrombolytic catheter (Uni*Fuse; AngioDynamics, Latham, NY) into the proximal part of the thrombus in such a way that a few proximal holes of the catheter aligned adjacent to the proximal end of the thrombus. Such placement of the catheter was practiced to ensure adequate lysis of the thrombus. After the sheath and catheter were secured with a skin suture, the patients were transferred to the inpatient unit. Per the standardized thrombolysis protocol, a bolus dose of 10 mg of recombinant tissue-type plasminogen activator (Actilyse; Boehringer Ingelheim, Ingelheim, Germany) in a saline solution (50 mL) was injected during 30 minutes, followed by continuous infusion of recombinant tissue-type plasminogen activator at a rate of 1.0 mg/h; 500 IU of unfractionated heparin was infused through the catheter every hour. During infusion, the fibrinogen level was monitored every 6 hours. Moreover, lysis was monitored with periodic angiography every 8 to 12 hours. The infusion was terminated at once if any adverse event was encountered. In the absence of any adverse event and fibrinogen levels of $1.5 g/L, infusion was continued either until the completion of treatment or maximum infusion time of 48 hours. In the case that fibrinogen levels decreased to <1.5 g/L, the rate of infusion was reduced to half. Patients were kept under
Journal of Vascular Surgery Volume
-,
Number
Lian et al
3
-
Fig 1. Angiographic images from left lower limb of a 78-year-old man who presented with acute severe ischemia. a, Occlusion of left popliteal artery as well as of tibioperoneal trunk. b, The thrombolysis catheter across the opened popliteal artery and tibioperoneal trunk. c, Complete revascularization of arteries after catheter-directed thrombolysis (CDT).
continuous surveillance to detect any eventual signs of hemorrhage, and hematocrit and hemoglobin counts were frequently monitored. Aspirin (100 mg/d), clopidogrel (75 mg/d), and a statin (atorvastatin, 20 mg/d) were prescribed to each patient on discharge. Study end points. The primary end points evaluated were primary patency and limb salvage. In patients who required bilateral thrombolysis, each limb was analyzed independently. Secondary end points were technical success, clinical success, target region revascularization, and periprocedural and postprocedural complications. Definitions and outcome measures. Acute lower limb ischemia was defined as the limb with ischemic symptoms of acute onset and duration of #14 days. The Rutherford classification was used to classify the clinical severity of ischemia (Table I).9 Primary patency and limb salvage were determined in concordance with the SVS guidelines.9 Additional endovascular procedures (balloon angioplasty) to obtain sufficient distal perfusion were recorded but not considered technical failure of the CDT procedure. The need for such additional procedures within the same hospital stay after thrombus dissolution with CDT was still defined as primary patency. Limb salvage was defined as freedom from major amputation and maintained functional autonomy (walking or
standing). Major amputation was defined as an amputation performed above the ankle. Target lesion reinterventions were classified as major (conversion to bypass, thrombectomy, thrombolysis, or major surgical procedure) or minor (new endovascular procedure without the need for thrombectomy or thrombolysis). Clinical success (improvement in clinical status) was assessed according to SVS guidelines as an improvement in Rutherford grade of at least one category (Table I) with objective evidence of hemodynamic change (0.1 increase in ankle-brachial index [ABI]).9 According to the guideline, marked improvement in clinical status (grade þ3) refers to limbs having no ischemic symptoms and any foot lesions completely healed; ABI essentially “normalized” (increased to >0.9) after intervention. Moderately improved (grade þ2) clinical status refers to limbs having no open foot lesions, still symptomatic but only with exercise, and improved by at least one category; ABI is not normalized but has increased by >0.1 after intervention. Minimally improved (grade þ1) clinical status refers to limbs having >0.1 increase in ABI but no categorical improvement or vice versa (ie, upward categorical shift without an increase in ABI of >0.1). The technical success was defined as residual target stenosis of <30% (by visual estimation) without flow-limiting target vessel dissection at completion
4
Journal of Vascular Surgery
Lian et al
---
2019
Table I. Clinical categories of acute limb ischemia (ALI) Findings Category I. Viable
Description/prognosis
Doppler signal
Sensory loss
Muscle weakness
Arterial
Venous
None
None
Audible
Audible
None
Inaudible
Audible
Mild, moderate
Inaudible
Audible
Profound, paralysis (rigor)
Inaudible
Inaudible
Not immediately threatened
II. Threatened a. Marginally
Salvageable if promptly treated
Minimal (toes) or none
b. Immediately
Salvageable with immediate revascularization
More than toes, associated with rest pain
Major tissue loss or permanent nerve damage inevitable
Profound, anesthetic
III. Irreversible
digital subtraction angiography after intervention.9 Complications were categorized according to the Society of Interventional Radiology classification system.11
Table II. Baseline characteristics and comorbidities of patients
Follow-up. Patients were followed up in the outpatient department at 30 days, 6 months, and 12 months. The condition of the treated limb was assessed on each visit with ABI and duplex ultrasound scanning combined with magnetic resonance angiography. Any complications including distal thromboembolism were noted during follow-up. Furthermore, the need for any additional procedure or conversion to open surgery was also recorded.
Age, years
Statistical analysis. All statistical analyses were performed with GraphPad Prism version 5.0 software (GraphPad Software Inc, San Diego, Calif). Continuous variables were reported as means 6 standard deviations, and categorical variables were shown as percentages. Primary patency and limb salvage were assessed by Kaplan-Meier survival methods. A value of P < .05 was considered significant for all statistical analyses.
RESULTS Baseline characteristics of patients. A total of 31 patients (33 limbs) with below-knee ALI underwent CDT during the study period. Six patients were lost to followup. On phone call inquiry, one was found to be deceased and two had major limb amputation at other hospitals. The remaining three could not be contacted. Finally, a total of 28 patients (30 limbs) were available for reporting after intervention. Demographic data and comorbidities of all the patients are outlined in Table II. Baseline lesion characteristics. Baseline lesion characteristics are summarized in Table III. There were four cases (13.33%) of Rutherford grade I, 15 (50.0%) cases of Rutherford grade IIa, and 11 (36.67%) cases of Rutherford grade IIb. With regard to etiology of ischemia, nine limbs had embolic etiology as suggested by abrupt severe symptoms with history of either arterial fibrillation or coronary artery disease and a relatively healthy arterial
Study group
Male/female Arterial hypertension
Patients (N ¼ 28) 65.13 6 10.0 (41-78) 19/9 (67.85/32.14) 19 (67.85)
Coronary artery disease
7 (33.33)
ESRD (Cr >150 mmol/L)
2 (7.14)
Diabetes
15 (53.57)
Smoking history
19 (67.85)
COPD HTN
4 (14.28) 19 (67.85)
CAD
11 (39.28)
Atrial fibrillation
11 (39.28)
Multiple comorbidities
6 (21.42)
CAD, Coronary artery disease; COPD, chronic obstructive pulmonary disease; Cr, creatinine; ESRD, end-stage renal disease; HTN, hypertension. Categorical variables are presented as number (%). Continuous variables are presented as mean 6 standard deviation (range).
tree without collateral formation on imaging analysis. Seventeen limbs had in situ thrombosis and four had thrombosed popliteal artery aneurysm. Five patients had a pedal runoff score of 0; 11, score of 1; 9, score of 2; and 5, score of 3. In this study, 12 limbs had good (<5), 10 limbs had compromised (5-10), and 8 limbs had poor (>10) runoff scores. Immediate outcomes. Technical success was achieved in 25 (83.33%) treated limbs. In the remaining patients not characterized as having technical success (n ¼ 5), aspiration with a syringe through a standard angiographic catheter was successful (n ¼ 2) and surgical revascularization was successful (n ¼ 2). Early amputation was needed in one limb after unsuccessful thrombolysis. Early termination of CDT due to any adverse event was not encountered in any patients. Additional endovascular procedures (angioplasty) were performed in 18 limbs (78.26%) on the completion of thrombolysis to obtain sufficient distal perfusion. The acute failure rates (failure
Journal of Vascular Surgery Volume
-,
Number
Lian et al
5
-
Table III. Baseline lesion characteristics Characteristics Duration of symptoms at presentation, days
Limbs 6.5 6 2.1 (3-14)
Severity (Rutherford grade)
Table IV. Catheter-directed thrombolysis (CDT)-related and overall 30-day complications CDT-related 30-day complications Minor (SIR A, B: nominal or no therapy, no consequence)
3 1
I (viable limb)
4 (13.33)
IIa (marginally threatened limb)
15 (50.0)
Major (SIR C, D, E: requires therapy or permanent sequelae)
IIb (immediately threatened limb)
11 (36.67)
Majorddeath (SIR F: death)
III (irreversible)
0
Etiology In situ thrombosis Thrombosed popliteal aneurysm Embolization
17 (56.67) 4 (13.33) 9 (30)
Previous ipsilateral revascularization Femoropopliteal (PTA/stent) Femoropopliteal bypass
3 0
0
All 30-day complications Minor (SIR A, B: nominal or no therapy, no consequence)
3
Major (SIR C, D, E: requires therapy or permanent sequelae)
2
Majorddeath (SIR F: death)
1
Majordamputation (SIR E: major amputation)
1
SIR, Society of Interventional Radiology.
Ischemic signs and symptoms Claudication
19
Pain at rest
11
Cold and mottled skin
14
Cool and cyanotic
16
Sensory deficit
19
Motor deficit Ischemic ulcer or gangrene
7 0
SVS runoff score Good (<5)
12 (40)
Compromised (5-10)
10 (33.33)
Poor (>10)
8 (26.67)
Pedal runoff 3
5 (16.67)
2
9 (30.0)
1
11 (36.67)
0
5 (16.67)
PTA, Percutaneous transluminal angioplasty; SVS, Society for Vascular Surgery. Categorical variables are presented as number (%). Continuous variables are presented as mean 6 standard deviation (range).
to traverse an occlusion or occlusion within 30 days) were 6.67% (2/30) of limbs, all of which had a poor runoff score before intervention. Clinical success was assessed according to the SVS guidelines-recommended scale for gauging changes in clinical status. Markedly improved clinical status (grade þ3) was achieved in 50.0% of limbs (n ¼ 15); moderately improved (grade þ2), in 43.33% of limbs (n ¼ 13); and minimally improved (grade þ1), in 6.66% of limbs (n ¼ 2). All the patients with minimally improved clinical status had a poor runoff score before intervention. Complications. All CDT-related and overall 30-day complications are listed in Table IV. The early (30-day) outcomes indicate that overall, 96.42% (n ¼ 27) of
patients were alive. One limb required early amputation (3.5%) after unsuccessful thrombolysis, as outlined before. The primary CDT group had four 30-day complications. There was one major complication of a significant retroperitoneal/groin hematoma; surgical decompression was performed with a successful clinical outcome. Three minor complications, all of which were postprocedural groin hematoma, were recorded. All the patients with groin hematoma received analgesia and were monitored in the inpatient department. These patients were not discharged until the hematoma subsided. There was one death and one major amputation reported at 30-day follow-up. Long-term outcomes. Primary patency for the entire cohort at 6 months and 12 months was 76.67% and 60.0%, respectively (Fig 2). Limb salvage was 90% at 6 months and 76.67% at 12 months (Fig 3). The patency rate at 6 months and 12 months was 91.67% and 83.33% for the good runoff group, 80% and 60% for the compromised runoff group, and 50% and 25% for the poor runoff group, respectively (Fig 4). The patency rate of the good runoff group was significantly higher compared with that of the poor runoff group (P ¼ .004). However, the compromised and poor runoff groups did not have significant difference in the patency rate (P ¼ .146) in this study (Fig 4). Freedom from recurrent symptoms (restenosis or occlusion) was 83.33%, 40.0%, and 25.0% at 12 months for the runoff score category good, compromised, and poor, respectively. The absolute numbers of restenosis (50.0%) and occlusion (25.0%) were higher in the poor runoff group. Major amputation rate was 37.50% and 20.0% at 12 months for the poor and compromised runoff groups, respectively. With regard to the etiology of lesions, embolic ALI had slightly better outcome with 66.67% (8/12) patent limbs compared with thrombosed ALI with 55.55% (10/18) patent limbs at 12 months. However, the difference was not statistically significant (P > .05).
6
Lian et al
Journal of Vascular Surgery ---
2019
Fig 2. Kaplan-Meier estimates of primary patency for the entire cohort at 12 months. Fig 4. Kaplan-Meier estimates of primary patency in each of the runoff score groups at 12 months. There was a significant difference in primary patency between the good runoff score group (green line) and the poor runoff score group (red line; P ¼ .004). However, there was no significant statistical difference in primary patency of the compromised runoff score group (blue line) compared with either the good runoff score group (green line) or the poor runoff score group (red line).
Fig 3. Kaplan-Meier estimates of limb salvage for the entire cohort at 12 months.
A total of two major amputations (6.67%) and one death (3.57%) were recorded during the 6-month follow-up period. A total of five major amputations (16.67%) and two deaths (7.14%) were recorded at 12 months of follow-up. The reintervention rate at 6 months and 12 months was 3.57% (one patient) and 21.42% (six patients), respectively.
DISCUSSION Despite the need of multiple procedures, interval care in a higher level nursing care unit, and risk of hemorrhage, CDT is one of the most commonly used and well-established techniques for ALI.12,13 More recently, several other endovascular techniques, like rotational thrombectomy and aspiration thrombectomy, as well as open techniques, like balloon embolectomy, have been reported either alone or in combination with CDT to achieve a higher technical success rate and longer patency rate. However, either the study group has a small subset of patients with popliteal and infrapopliteal lesions or the study did not report the efficacy for infrapopliteal lesions.3,4,14,15 Exact status of the CDT procedure specifically for popliteal and infrapopliteal thromboocclusive lesions has not been documented.16-20 Rheolytic thrombectomy (AngioJet) has been reported to be successful in approximately half of cases as a stand-
alone technique. Moreover, it has been found to be only marginally effective in clearing more organized thrombus.3 In a previous study that used rheolytic thrombectomy to treat below-knee thromboembolism, it was found that 43% of the cases required stent to achieve technical success. Moreover, the revascularizations were complicated by further distal embolization in 10%.4 Although rheolytic thrombectomy achieved 70% successful revascularization for thromboembolism in a study by Ansel et al,5 that study had only a small subset of patients who presented with primary occlusions distal to the popliteal artery. In addition, almost half required post-thrombectomy thrombolytic infusion. Aspiration thrombectomy may also be attempted as a standalone technique. However, suction thrombectomy requires the delivery of large-bore catheters to the level of the thrombus in small lower extremity arteries with concomitant risks of spasm, dissection, vessel rupture, and plaque disruption.3 In this study, we established the efficacy of CDT therapy for popliteal and infrapopliteal thrombo-occlusive lesions. The study demonstrated that CDT can be performed with robust technical success for acute popliteal and infrapopliteal vessel thromboembolism. Technical success was achieved in 83.33% of the patients in this study. Patency rate and limb salvage at 12 months were 60.0% and 76.67%, respectively. Furthermore, in this study, we used a modified Rutherford scoring system that incorporated both the distal popliteal and individual runoff scores. This allowed us to quantify the contribution of both the popliteal artery and the tibial vessels to measure procedural success. The patency
Journal of Vascular Surgery Volume
-,
Number
Lian et al
7
-
rate was found to be incrementally curtailed by worsening runoff, with significant decreases as runoff category deteriorated. This finding is in accordance with Davies et al.21 In addition, with regard to safety, the study reconfirmed that CDT can be performed relatively safely from the perspective of complications. In smaller vessels, treatment of thromboembolic occlusion is challenging and can be associated with considerable morbidity and mortality if they are not adequately addressed. Passage of large-bore catheters to carry out these endovascular procedures in small vessels increases the risks of spasm, dissection, vessel rupture, and plaque disruption. Furthermore, most of these procedures are complicated by angiographically evident distal thromboembolic complications despite the use of distal protection.3 Distal embolism was also a concern in this study. Most patients displayed signs of perfusion deterioration, sometimes accompanied by severe pain requiring opiates, during thrombolysis. However, the symptoms were relieved with ongoing thrombolysis. This phenomenon might be due to dislodging of thrombus and possible embolism, but no severe complications secondary to it were reported. We believe the CDT technique adopted in this study might be the reason for this.20 Infusing the thrombolytic agent through the entire length of the thrombus may cause uncontrolled distal thrombus disruption and possible distal embolism. Instead, the technique adopted in this study, whereby thrombolytic agent is not infused through the entire thrombus but only to the proximal portion of the thrombus, protects against possible distal embolism. In this technique, the thrombus dissolves gradually at the proximal part and collateral flow through the previously occluded side branches occurs, whereas the distal portion of thrombus provides natural embolic protection distally. Therefore, these small emboli tend to migrate to these side branches. Thus, this study demonstrated that CDT can reach small vessels and can cause enzymatic dissolution of the thromboembolism without any substantial risk of distal or proximal embolism, vessel injuries, or dissection. In contrast to CDT, open surgical thrombectomy of small vessels is associated with higher risk and difficulties. Surgical thrombectomy of the tibial vessels often requires selective over-the-wire passage of Fogarty catheters into the affected vessel, which can be cumbersome through open approaches. If it is done from the common femoral artery with use of smaller diameter balloon catheters, the diameter of the larger superior femoral artery may lead to loss of the thrombus during retrieval despite proximal vessel clamping and cessation of antegrade flow. Distal approaches through pedal artery cutdown are also effective but require closure of the smaller dorsalis pedis or posterior tibial arteries, risking postsurgical vessel stenosis. In addition, open thrombectomy is considerably more invasive and is typically associated
with a much more substantial perioperative recovery than is typically seen after percutaneous revascularization.3 Therefore, the importance of CDT stands out for thromboembolism involving smaller vessels, and our study has reconfirmed it by achieving better technical and longer patency rates with no serious complications. Admittedly, several limitations to the study may exist. The study was a single-arm trial with no control group. The number of patients included in the study is small, and therefore the power to detect differences in outcome may be insufficient. Thrombolysis in the study was carried out using a single-dose strategy and cannot be compared directly with other thrombolytic studies using different thrombolytic strategies.
CONCLUSIONS CDT provides excellent treatment results with an acceptable complication rate in treatment of popliteal and infrapopliteal artery thromboembolic lesions. Thus, CDT might be considered in the treatment of smaller vessel ALI if adequate periprocedural care and 24/7 inpatient unit services are provided. We thank Morgan A. McClure, a medical editor at North Sichuan Medical College, for English grammar correction and revision.
AUTHOR CONTRIBUTIONS Conception and design: WL, SD, XX, ML Analysis and interpretation: WL, SD, XX, ML Data collection: WL, SD, XH, XZ Writing the article: SD Critical revision of the article: WL, XH, XZ, XX, ML Final approval of the article: WL, SD, XH, XZ, XX, ML Statistical analysis: SD Obtained funding: Not applicable Overall responsibility: ML WL and SD contributed equally to this article and share co-first authorship.
REFERENCES 1. Walker TG. Acute limb ischemia. Tech Vasc Interv Radiol 2009;12:117-29. 2. Theodoridis PG, Davos CH, Dodos I, Iatrou N, Potouridis A, Pappas GM, et al. Thrombolysis in acute lower limb ischemia: review of the current literature. Ann Vasc Surg 2018;52:255-62. 3. Landau D, Moomey C, Fiorella D. First-in-man experience with the ReVive PV peripheral thrombectomy device for the revascularization of below-the knee embolic occlusions. J Endovasc Ther 2014;21:747-54. 4. Spiliopoulos S, Katsanos K, Fragkos G, Karnabatidis D, Siablis D. Treatment of infrainguinal thromboembolic complications during peripheral endovascular procedures with AngioJet rheolytic thrombectomy, intraoperative thrombolysis, and selective stenting. J Vasc Surg 2012;56: 1308-16.
8
Journal of Vascular Surgery
Lian et al
---
5. Ansel GM, George BS, Botti CF, McNamara TO, Jenkins JS, Ramee SR, et al. Rheolytic thrombectomy in the management of limb ischemia: 30-day results from a multicenter registry. J Endovasc Ther 2002;9:395-402. 6. Working Party on Thrombolysis in the Management of Limb Ischemia. Thrombolysis in the management of lower limb peripheral arterial occlusionda consensus document. J Vasc Interv Radiol 2003;14:S337-49. 7. Norgen L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45:S5-67. 8. Pereira CE, Albers M, Romiti M, Brochado-Neto FC, Pereira CA. Meta- analysis of femoropopliteal bypass grafts for lower extremity arterial insufficiency. J Vasc Surg 2006;44:510-7. 9. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517-38. 10. Byrne RM, Taha AG, Avgerinos E, Marone LK, Makaroun MS, Chaer RA, et al. Contemporary outcomes of endovascular interventions for acute limb ischemia. J Vasc Surg 2014;59:988-95. 11. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003;14:S199-202. 12. Ouriel K, Shortell CK, DeWeese JA, Green RM, Francis CW, Azodo MV, et al. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 1994;19:1021-30. 13. Berridge DC, Kessel DO, Robertson I. Surgery versus thrombolysis for initial management of acute limb ischaemia. Cochrane Database Syst Rev 2013;6:CD002784. 14. Shammas NW, Dippel EJ, Shammas G, Gayton L, Coiner D, Jerin M. Dethrombosis of the lower extremity arteries using
15.
16.
17.
18.
19.
20.
21.
2019
the power-pulse spray technique in patients with recent onset thrombotic occlusions: results of the DETHROMBOSIS Registry. J Endovasc Ther 2008;15:570-9. Saxon RR, Teigen C. Novel thrombectomy system for below-the-knee and visceral arterial interventions: PRISM retrospective interim results. J Vasc Interv Radiol 2015;26: 149-50. Grip O, Kuoppala M, Acosta S, Wanhainen A, Åkeson J, Björck M. Outcome and complications after intraarterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion. Br J Surg 2014;101: 1105-12. Schrijver A, de Vries JP, van den Heuvel DA, Moll FL. Longterm outcomes of catheter-directed thrombolysis for acute lower extremity occlusions of native arteries and prosthetic bypass grafts. Ann Vasc Surg 2016;31:134-42. ski S. Safety Falkowski A, Poncyljusz W, Samad RA, Mokrzyn and efficacy of ultra-high-dose, short-term thrombolysis with rt-PA for acute lower limb ischemia. Eur J Vasc Endovasc Surg 2013;46:118-23. Pascoe H, Robertson D. Catheter directed thrombolysis for acute lower limb ischaemia: an audit. Australas Med J 2014;7:471-5. Lukasiewicz A, Lichota W, Thews M. Outcomes of accelerated catheter-directed thrombolysis in patients with acute arterial thrombosis. Vasc Med 2016;21:453-8. Davies MG, Saad WE, Peden EK, Mohiuddin IT, Naoum JJ, Lumsden AB. Impact of runoff on superficial femoral artery endoluminal interventions for rest pain and tissue loss. J Vasc Surg 2008;48:619-25.
Submitted Nov 6, 2018; accepted Mar 19, 2019.