Cyanoacrylate Closure (CAC)

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R. Singh and V. Ojha

Complications Minor complications of sclerotherapy

include leg swelling, local site pain, skin pigmentation (11–30%), erythema and neural injuries (0.2%) and venous thrombus embolism (0.1–0.2%). Other rarer complications include supercial thrombophlebitis (~4.4%), dermal necrosis, compartment syndrome, haemoglobinuria and cardiopulmonary collapse [16].

Cyanoacrylate Closure (CAC)

Intravenous CAC was also approved for endovenous ablation by the FDA in 2015. This non-thermal procedure does not require anaesthesia and uses N-butyl cyanoacrylate (NBCA) for venous thrombosis. The vascular access for CAC ablation is taken with 7Fr sheath followed by the advancement of 5Fr delivery catheter ~3–5cm distal to the saphenofemoral junction. 0.1–0.3mL CAC is delivered at 2–3cm step along the abnormal vein, and compression under USG guidance is done at each venous segment.

The CAC glue undergoes polymerization and initiates inammation in the venous wall on contact with blood [17]. Complication of CAC ablation includes supercial phlebitis (glue—irritant). But instances of peri-procedural pain, burn marks, paraesthesias, ecchymoses, and pigmentation are less common compared to thermal ablative methods [18].

NBCA is found to be superior in terms of improvement of VCSS scores and recovery time as compared to thermal ablative methods.

Mechanochemical Ablation (MOCA)

Mechanochemical ablation is a non-thermal method of venous ablation which uses a combined technique comprising of mechanical injury of venous wall by rotating wire and chemical injury to the injured venous wall by simultaneous injection of sclerosing agent (chemical) [19]. This procedure doesn’t require administration of tumescent anaesthesia. The ClariVein (the rst MOCA device) consist of a motor handle which rotates the wire and is also attached to the syringe containing sclerosing agent. Wire rotation in the targeted vein causes vascular spasm which is followed by continued delivery of sclerosant in a spinning manner. MOCA is found very effective with less post-procedural complications on short-term follow-up.

Cryosclerosis

This method of non-thermal ablation was introduced in 1981 by Milleret and Le Pivert [20]. In this, a cryo-probe is passed within a varicose vein, after local anaesthesia administration tip of cryo-probe is frozen up to 89°C which causes venous wall injury with resultant thrombosis and brosis. It has been found that this method of venous ablation does not lead to signicant peri-procedural pain [20].

27.4 Deep Vein Thrombosis

Deep vein thrombosis (DVT) is a preventable cause of signicant patient morbidity and in-hospital mortality all over the globe. The incidence of thromboembolism of venous origin (VTE) is approximately 1/1000 individuals per year, with DVT accounting for approximately two-thirds of these cases [21]. The presentation of deep vein thrombosis varies signicantly and is usually on-specic. But the suspicion of DVT based on non-specic clinical features is important as it determines the pre-test probability of DVT.

The usual presentation of acute deep vein thrombosis includes calf pain and tenderness in the lower limb, which may show insidious progression proximally.

27.4.1 Diagnosis

27.4.1.1 Pre-Test Probability

In patients who are suspected to have DVT, the Wells rule assists in calculating pre-test probability and guiding further management. It classies individuals into “unlikely” (≤1 point) to have DVT or “likely” (≥2 points) to be having DVT [22]. It also helps the clinicians in determining whether an alternative diagnosis of patient symptomology is possible or not, as both these groups will require different management.

Among patients with suspected DVT admitted in hospital, radiological assessment is needed because Wells rule

and clinical assessment do not hold value in such cases and D-dimer values show signicant false positive values.

27.4.1.2 D-Dimer Assessment

D-dimer values are increased in most patients who are positive for DVT (sensitivity reaches up to 96%) but is very nonspecic (42–52%) as it is raised in older patients, cancer, infection, inammatory conditions, chronic renal failure, recent operation/trauma, burns and pregnancy [23]. When a

D-dimer test is negative and the patient has a low to moderate pretest clinical probability, the likelihood of DVT and PE is low and precludes the need for imaging studies.

However, if there is a higher clinical pretest probability for acute pulmonary imaging, further radiological assessment

should be done instead of performing a non-specic screening D-dimer test.

27.4.1.3 Radiological Evaluation

Radiological evaluation is employed to conrm DVT.USG is the investigation of choice for conrmation of DVT since it is non-invasive, easily available, reliable and does not involve radiation exposure [24]. Sonography (Fig.27.5) can assess the extent, age and degree of luminal occlusion and plan management accordingly with good accuracy [25].

27 Interventions oftheExtremity Veins

ab c

339

Fig. 27.5 A 21-year-old male patient presented with right lower limb swelling and pain for the last 2weeks prior to presentation. USG right lower limb showed hypoechoic thrombus extending from common iliac vein (CIV) (yellow asterisk) into external iliac vein (EIV) (red asterisk),

Other diagnostic modalities which can be used in DVT include conventional venography and CT venography. Conventional venography (Fig.27.6) is the gold standard investigation in lower limb DVT, but is not used because of its invasive nature, limited availability and availability of less invasive CT venography [26]. A lling defect which is persistent in multiple projections is taken as diagnostic for deep vein thrombosis [35].

CT venography is an easily available, very sensitive and specic investigation for DVT with the benet of multiplanar imaging [27]. But it carries ionizing radiation exposure risk and is contraindicated if the patient has renal insufciency and contrast hypersensitivity.

27.4.2 Indications forIntervention

Most patients with acute lower limb DVT are treated with anticoagulation alone. Few studies have shown better resolution of thrombus with systemic delivery of thrombolytic agents than with anticoagulation alone, even long-term, but with unacceptable bleeding risk with systemic delivery. The Society of Interventional Radiology in its guidelines mentions a subset of patients who may benet from a strategy of early thrombolysis in DVT.They include

1. Healthy patients with good longevity having iliofemoral

DVT.

2. Patients with markedly severe symptoms (i.e. massive

swelling, phlegmasia cerulea dolens).

common femoral vein (CFV) (white asterisk) up to popliteal vein (PV). The involved venous segments were dilated and showed patchy colour ows (a–c)

inactive and have diminished longevity should be treated with anticoagulation alone [28].

In general, the earlier thrombolytic treatment is applied, the more likely is the treatment to be successful. As the thrombus ages and becomes chronic, it becomes more difcult to treat [29]. When early thrombus removal is indicated, it is recommended to use an approach consisting of either catheter-directed thrombolysis (with or without percutaneous mechanical thrombolysis) over systemic thrombosis.

27.4.3 Thromboreductive

Therapies—Rationale

Systemic Thrombolysis It refers to dissolution of thrombus

with a thrombolytic agent administered by peripheral route. Systemic thrombolysis with rt-PA for acute DVT has been evaluated extensively and is considered in certain individuals after a thorough clinical assessment of patient eligibility for systemic thrombolysis.

27.4.4 Patient Selection—Anatomic

andClinical Considerations

Expected Risk of Bleeding All patients are thoroughly evaluated for factors which increase the risk of major bleeding [29]. Systemic thrombolysis decisions should be individualized from case to case after assessing the clinical severity of DVT.

Patients with isolated distal DVT involving calf veins

should be treated with anticoagulation alone. Similarly, older patients with other morbidities who are bedridden or

Clinical Severity of DVT Patients should be evaluated carefully to assess what is the primary goal of active endovascular intervention in DVT like whether it is to prevent

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R. Singh and V. Ojha

abc

Fig. 27.6 Diagnostic cavogram shows ecstatic infrarenal and juxtarenal IVC (Straight white arrow) (max diameter 28mm) with no evidence of thrombus (a). Diagnostic venogram shows extensive thrombus

complications of acute DVT, or there is signicant proximal DVT progression, or increased clinical severity and/

or failure of initial anticoagulant therapy.

Anatomical Extent Acute iliofemoral DVT patients are

signicantly associated with post-thrombotic syndrome and recurrent venous thromboembolism, and decisions regarding endovascular intervention should be made from case to case in acute iliofemoral DVT [30]. In femoropopliteal DVT which does not involve CFV, thrombolysis is considered in very symptomatic individuals with very low bleeding risk.

Life Expectancy and Underlying Co-Morbidities Systemic thrombolysis is not considered in individuals with low life expectancy and who are bedridden. Anticoagulation alone should be considered in these patients.

27.4.5 Endovascular Interventions forDVT

27.4.5.1 Catheter-Directed Thrombolysis

It involves intra-thrombus administration of thrombolytic agent like rt-PA with multiple side-hole catheter to attain a good local thrombolytic concentration and ensures thrombolysis with a lesser thrombolytic dose [31].

In this technique, ultrasound guidance provides access to the affected lower limb deep veins. After attaining vascular access, venography is done to determine the thrombus extent. A catheter is advanced within the thrombus and infusion of rt-PA given @ of 0.01 mg/kg/h increased up to a max of

extending from the right distal common iliac vein up to the left popliteal vein causing up to 80–90% luminal stenosis (black arrow) (b). No evidence of thrombus in the proximal left CIV (yellow asterisk) (c and d)

1 mg/h or reteplase @ 0.25 to 0.050 U/h is started. The thrombolytic drug is infused for a duration of 6–24h. The patient is monitored continuously for major bleeding episodes, and a repeat venogram is done. The multi side-hole catheter is repositioned to advance it into the remaining thrombus to further continue the infusion. Once acute thrombus is lysed, venography is repeated for any venous stenotic/ obstructive and is treated with angioplasty and/or stenting [31].

The main limitation of the original CDT is the long tiring infusion duration usually consisting of 1–3days needed to achieve adequate thrombolysis of extensive DVT.This long duration of infusion causes a signicant burden on health resources usage and increased risk of major internal bleeding. Accounting to these limitations, there has been signicant advancement in CDT techniques for dealing with limitations with conventional CDT methods.

One method of dealing with this limitation is using low-power USG energy which serves to scatter the thrombolytic agent within the thrombi by using an USG-emitting thrombolytic infusion catheter [32]. The supposed advantages are

(a) Relatively rapid thrombolytic drug administration at low

dose.

(b) Better preservation of valvular apparatus due to the abil-

ity of the ultrasound energy to access perivalvular thrombus.

ratus and greater clinical practice efciencies.

27 Interventions oftheExtremity Veins

341

27.4.5.2 Pharmacomechanical CatheterDirected Thrombolysis (PCDT)

It combines the usage of catheter-directed thrombolysis and pharmacomechanical thrombolysis (PMT). This new hybrid technique has increased the CDT’s ability to remove large thrombi and is based on the principle that pharmacomechanical thrombolysis accentuates the surface area of thrombus and fastens pharmacological thrombolysis (Figs. 27.7 and

27.8). Further, with PMT the drug dose and total infusion

duration can be decreased with resultant low major bleeding complications, and CDT in PCDT serve the function of dissolving the PMT-created thrombi fragments which can cause pulmonary embolism if not removed. Depending on the type of dosing, choice of devices and methods of use, at present it may be simplest to conceive of two categories of pharmacomechanical catheter-directed thrombolysis.

Fig. 27.7 Pharmacomechanical thrombolysis of involved venous segments was performed using alteplase (15mg/100ml saline) infused via AngioJet (8F) catheter system for a duration of 30min. Check angiogram showed up to 80% resolution of the thrombus in the popliteal vein

Fig. 27.8 Subsequently, pharmacological infusion (heparin via the vascular sheath + alteplase via Cargg-McNamara catheter) was continued for 12h. Final check angiogram revealed 80–90% resolution of the thrombus in left SFV, CFV, EIV and CIV (a–c) with smooth short seg-

and supercial femoral vein (white straight arrow) (a) and up to 40% resolution of thrombus in the left CFV, EIV and CIV on subsequent venogram (b–d)

ment stenosis (black asterisk) of right CFV.Balloon dilation of stenosed CFV was done with 10×60 and 12×40mm balloons and was unsuccessful with signicant residual stenosis of right CFV (d). Patient was discharged on anticoagulation

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R. Singh and V. Ojha

First-Generation Pharmacomechanical CatheterDirected Thrombolysis

This generation uses mechanical thrombectomy along with infusion CDT—it relies on gradual thrombus dissolution, and the intent is to fasten the process and reduce the drug dose. Two forms of rst-gen PCDT which have been used are:

1. “Infusion-rst PCDT” includes the use of a CDT infu-

sion followed by PMT (provided with/without an aspirational device) at f/u staged session to break, remove and aspirate any residual thrombi.

2. The other method of rst-generation PCDT includes the

buzz-lyse method which uses an aspiration device to macerate the thrombus rst followed by catheter-directed thrombolysis infusion. It has been found previously that rst-generation PCDT results in good intervention safety and thrombolysis efcacy which is found to be similar to CDT alone. Further with PCDT, there has been ~40–50% decrease in drug dose, treatment time, hospital stays and expenses compared with traditional CDT [33].

Single-Session (Second-Generation) Pharmacomechanical Catheter-Directed Thrombolysis

This generation of CDT involves different techniques which are capable of delivering the thrombolytic agent into the thrombus to ensure complete thrombolysis in a single session consisting of 2–3 h. Since complete thrombolysis is achieved in this period, there is no need for prolonged thrombolytic infusion.

Out of three commonly used techniques, two techniques

use AngioJet in this method of PCDT.

ences with these endovascular intervention techniques conveyed that adequate thrombolysis is achieved in up to 90% of patients, and 50–80% of these individuals can be treated in one session.

27.4.5.3 Endpoint Assessment forEndovascular Thrombolysis

The long-term clinical objective of endovascular thrombolysis is to prevent PTS via:

(a) Prevention of recurrent DVT. (b) Maintenance of long-term venous patency. (c) Venous valvular preservation of venous valvular

function.

So the “open vein hypothesis” holds here too which states that early thrombolysis and the resultant patent venous system will contribute to achieving these goals in patients of DVT.

27.5 Endovascular Therapy forAcute

Pulmonary Embolism

Acute pulmonary embolism (PE) is the third most common cause of death among hospitalized patients. Escalation of treatment beyond anticoagulation therapy is necessary in patients with massive PE (haemodynamic shock) as well as in many patients with submassive PE (right ventricular strain).

27.5.1 Pulmonary Embolism (PE)

1. With the “power pulse” method, AngioJet forcefully does pulse-spraying of a bolus of thrombolytic agent into the thrombi [34]. The thrombolytic agent is made to disperse in thrombi for half an hour. This is followed by aspiration of remaining thrombus with AngioJet.

2. Second is “rapid lysis” technique, which involves simultaneous infusion of the thrombolytic drug and aspiration of thrombus with AngioJet [35].

3. The third technique consisting of single-session phar-

macomechanical catheter-directed thrombolysis is “isolated thrombolysis,” which is performed with Trellis

infusion system [36]. This infusion system consists of balloons which are catheter-mounted and serve the function of isolating the thrombosed vein to be thrombolysed. After this, a bolus of thrombolytic agent is administered into isolated thrombosed vein. This drug delivery is followed by oscillating wire activation for 7–11min which serves the function of mechanical distribution of the drug in thrombi followed by aspiration. Initial reported experi-

Acute massive pulmonary embolism is a life-threatening subset of venous thromboembolism and is dened as proximal pulmonary embolism complicated with haemodynamic instability and shock. It represents the most fatal form of venous thromboembolic disease. The mortality rate can exceed 60% in acute massive pulmonary thromboembolism, and most of them occur within a few hours of initial detection [37]. The details of pulmonary embolism are also covered in Chap. 19.

27.5.2 Clinical Features

Clinical presentation is usually non-specic and presents with dyspnoea and acute onset of atypical chest pain. Patients can also experience pleuritic chest pain with haemoptysis (if pulmonary infarction occurs). In addition, there can be nonspecic features like increased heart rate, fast breathing, pyrexia and sudden onset of cough. The suspicion of massive

27 Interventions oftheExtremity Veins

343

pulmonary embolism should be kept in mind if a patient presents with sudden onset of loss of consciousness, hypotension, extreme hypoxemia and cardiac arrest [38].

27.5.3 Imaging Evaluation

Conventional angiography is the best investigation in diagnosing pulmonary embolism, but considering its invasive nature, lesser availability and time-consuming nature, CT pulmonary angiography (CTPA) is the investigation of choice for pulmonary embolism. It is the preferred noninvasive modality because of rapid acquisition, higher spatial and contrast resolution and ability to visualize segmental and sub-segmental branches with the highest sensitivity and specicity for PE diagnosis.

27.5.4 Management

Acute massive pulmonary embolism can cause right ventricular failure with resultant decreased left ventricular preload and haemodynamic shock (systolic blood pressure [SBP] <90mm of Hg).

bolysis in emergency setting and associated high fatality rates. In these conditions, an endovascular approach consisting of catheter-directed thrombolysis with tPA is considered [41], and the indications for active endovascular intervention in PE (at Least One) are as follows:

1. Cardiogenic shock.

2. Circulatory collapse.

3. 2D Echocardiography demonstrating RV strain and/or PAH

4. C/I to thrombolysis/anticoagulant in clinically severe PE.

Catheter-directed thrombolysis can be used to augment the thrombolytic process if there is a failure of systemic thrombolysis or ongoing thrombolysis [42].

The dose of IV thrombolytic can be reduced by at least 50% if CDT is started actively, which allows withdrawal of alteplase within 1hour and reduces the risk of bleeding [43]. In a meta-analysis consisting of 594 individuals of PE managed with CDT, there was haemodynamic stabilization, oxygen saturation improvement and increased survival rate in

86.5% cases. Further, there is a decreased dose of tPA used in CDT compared to systemic thrombolysis with a resultant lesser risk of bleeding which has been estimated up to 2.4% with CDT in the literature [42].

1. For hypotension: Normal saline infusion to be done with care, and dopamine should be initiated if hypotension persists.

2. For respiratory failure: O2 inhalation→ intubation→

mechanical ventilation.

3. Anticoagulant: The aim of anticoagulant in PE is to prevent thrombus progression, decrease thrombotic burden, and let the patient’s thrombolytic system work. Parenteral anticoagulation with heparin (LMW), UFH and fondaparinux is started until there is no contraindication to anticoagulation [38]. If the clinical suspicion of pulmonary embolism with haemodynamic instability is very high, it is advised to start i.v. anticoagulation prior to imaging [38].

4. Systemic thrombolytic therapy: The most common and widely accepted indication for systemic thrombolysis in pulmonary thromboembolism is haemodynamic instability/shock. Currently, the approved thrombolytic agent for acute massive pulmonary embolism is 100mg of alteplase (rt-PA) which is infused intravenously for a duration of over 2h [39].

5. Endovascular intervention: Despite the fact that sys- temic thrombolysis is indicated for the treatment of acute massive PE, many patients are not eligible for systemic thrombolysis due to absolute contraindications and the associated high risk of bleeding ~20%, which include a 3–5% risk of intracranial bleed [40]. In addition, there is a time constraint to infuse the whole dose of IV throm-

27.5.5 Endovascular Techniques

CDT for pulmonary embolism uses catheters (<10 French) which cause mechanical debulking and aspiration of thromboemboli and also intra-clot thrombolytic injection. Based upon the expected future bleeding risk with CDT, it should be done with either mechanical debulking or lesser dose of local tPA delivery. The aim of all CDT is to fasten thrombolysis to remove the RV strain, increase pulmonary blood ow through the thrombus, and increase the surface area to which thrombus is exposed by local thrombolytic infusion.

Several devices for CDT in PE are being used, but the most frequently employed technique is the rotating pigtail fragmentation. This technique can be used alone or in combination [44]. Although this technique is effective in debulking the proximal thrombus, it carries the risk of distal thromboembolism. This can require performing additional aspiration [45]. Aspiration thrombectomy can be done with any end-hole catheter. Thus, it can be inferred there was a need to have additional methods for use with rotating pigtail fragmentation. The major benet of the pigtail fragmentation method is easy availability and lesser cost compared to commercially available mechanical thrombectomy devices.

Mechanical thrombectomy devices which are available in market for use in pulmonary embolism include AngioJet Rheolytic Thrombectomy (ART), Amplatz Thrombectomy Device and Aspirex. The use of AngioJet Rheolytic

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Thrombectomy (ART) is found to be associated with signicantly increased complications including haemoglobinuria, arrhythmias, renal insufciency, complete heart block, signicant haemoptysis and even sudden cardiac death [44].

The Helix Clot Buster, i.e., Amplatz Thrombectomy Device (ATD), is conventionally approved for thrombosis in dialysis, grafts and AV stulas but can be used to treat acute PE.Its use in mechanical thrombectomy has not been associated signicantly with haemolytic adverse events as in ART [46].

There is a new device developed for use in PE recently, the Aspirex based on Archimedes’ screw principle. The device causes fragmentation of thrombus followed by electrical activation of coils within this device. This results in thrombus aspiration from the tip of the catheter, which carries the thrombus into the collecting system [47].

Regardless of the type of endovascular intervention which is performed for thrombolysis in acute pulmonary embolism, it is the haemodynamic improvement after intervention which should be used as a guide to the success of thrombolytic interventions without considering the angiographic ndings [48]. If additional thrombolysis can be done without major bleeding, catheter-directed thrombolysis can be prolonged in case of elevated PA pressure with RV strain pattern. It has been found that the advantage of prolonged thrombolysis is to continue the clot lysis process and decrease the future risk of chronic pulmonary thromboembolism and resultant PAH.

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Endovascular Interventions inHemodialysis Access Fistulas

JineshValakkada, AnoopAyyappan, andVimalChackoMondy

Key Messages

1. The number of patients on dialysis by AV stulas and stula-related complications is on a rising trend.

2. Arteriovenous stula is prone to multiple complications like lack of maturation, venous stenosis, thrombosis, venous pseudoaneurysms, and central vein obstruction.

3. Hemodynamic and physiological changes in end-stage renal disease (ESRD) patients need to be kept in mind during endovascular interventions.

4. Early stula malfunction is mostly caused by venous stenosis, which generally occurs beyond the arteriovenous anastomosis.

5. Treatment for venous stenoses includes high- and ultrahigh- pressure venoplasty, cutting balloon venoplasty, and bare stent placement.

6. Acute stula thrombosis requires declotting by thrombolytics or mechanical devices and further venoplasty if underlying stenosis is the precursor of the thrombosis.

7. Central venous stenosis presents as limb edema and requires angioplasty or stent placement to relieve the obstruction.

8. Distal hypoperfusion ischemic syndrome presents as ischemic symptoms and requires surgical revision in a majority of cases, though new endovascular options are there.

9. Surgical treatment is required in infected grafts, large venous aneurysms, and in stenosis which fail to endovascular treatment.

J. Valakkada (*) · A. Ayyappan · V. C. Mondy Department of Imaging Sciences and Interventional Radiology, Sri Chitra Tirunal Institute of Medical Science and Technology, Thiruvananthapuram, India

28.1 Introduction

End-stage renal disease (ESRD) causes signicant morbidity in adults. It is increasing in incidence with around 232 per million patients every year requiring renal replacement therapy (RRT) [1–3]. Though renal transplantation is the denitive treatment, lack of donor availability and high economic cost are major issues [4]. Arteriovenous stula (AVF) is the most common mode of RRT.However, AVFs are associated with many complications that require surgery or intervention causing a signicant cost burden on the patients. Active surveillance is essential to facilitate the early identication of complications. Physical examination and Doppler imaging are used to identify an early failing stula [5]. Endovascular interventions play a major role in access-related complications of AVF.

28.2 Anatomy ofAV Fistula

In chronic kidney disease, AVF needs to be created at least 6months before the expected period of end-stage renal disease so that the stula is matured by the time RRT is required [6]. There are two types of AVFs: native, which is created by direct anastomosis between a native artery and vein, and graft AVF, which is created by using a prosthetic material (graft) between artery and vein (in case the vein is not suitable for direct anastomosis). Even though the maturation of graft is instantaneous, native AVFs are preferred over graft AVFs due to longer patency rates and lower infection rates [5]. Native AVFs include radiocephalic stula (RCF), brachiocephalic stula (BCF), and brachial transposed basilic vein stula (BTB) and are created preferably in the nondominant upper limb (Fig.28.1) [5, 6]. Lower limb AVFs have a higher rate of infection and thrombosis and are used only if upper limb veins are unsuitable for stula.

Radiocephalic stula (RCF) is the preferred site since it is easy to create, preserves the future option of creating more proximal BCF, and is associated with a low rate of

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