Adenosine-induced transient circulatory arrest in transvenous embolization of cerebral arteriovenous malformations

Abstract

Due to advances in interventional techniques, the transvenous approach may present an effective treatment option for embolization of brain arteriovenous malformations (AVMs). Contrary to the transarterial method, the transvenous approach can only be utilized in a specific subset of patients and is not suitable as a standard procedure for all AVM lesions. While this technique can be helpful in certain patients, careful patient selection to ensure patient safety and favorable clinical outcomes is important. However, especially in high-flow AVMs, targeted deposition of embolic materials through a transvenous access can be challenging. Therefore, a temporary flow arrest may prove helpful. Transient cardiac arrest by use of adenosine has been applied in cerebrovascular surgery but is not common for endovascular embolization. Adenosine-induced arrest and systemic hypotension may be a feasible, safe method to reduce flow and help endovascular transvenous embolization of certain AVMs. Our study evaluated the efficiency and safety of adenosine-induced circulatory arrest for transvenous embolization of cerebral AVMs.

Introduction

Cerebral arteriovenous malformations (AVM) are vascular lesions with abnormal connections between arteries and veins in form of a so-called nidus.^1,2 The signs and symptoms of AVMs include headaches, seizures, progressive neurological deficits and hemorrhage. ³ The annual risk of hemorrhage is 1.5–2%, ⁴ and the risk of re-bleeding within 1 year after the first hemorrhage is 2–18%. ⁵

Treatment options include surgical resection, endovascular embolization, radiosurgery, or a combination of these modalities. The treatment decision depends on location, signs and symptoms, and vascular anatomical structure of the AVM.^6,7 Endovascular embolization and radiosurgery can be carried out as primary treatments or to reduce the nidus size and facilitate surgical resection. ⁸

The treatment goal is to close the nidus while maintaining the patency of the venous drainage. Traditionally, the transarterial route has been used for endovascular embolization of AVMs. However, the transvenous method can be helpful if the transarterial access is inadequate, for example with tiny perforating feeders. ⁹ Owing to advances in interventional techniques, the transvenous approach may present an effective treatment option for AVMs in certain cases. However, especially in high-flow AVMs, targeted deposition of embolic materials through a transvenous access can be challenging. Therefore, a temporary flow arrest may prove helpful. This can either be achieved by balloon occlusion or by systemic hypotension. The use of adenosine has been described for clipping of cerebral aneurysms when temporary clipping was not possible or during intra-operative aneurysm rupture. In recent years, it has also been used for endovascular procedures such as thoracic aortic aneurysms, coronary stenting and AVM embolization. ¹⁰

The aim of our study was to evaluate the efficiency and safety of adenosine-induced circulatory arrest for transvenous embolization of cerebral AVMs.

Methods

We included six patients with ruptured AVMs who underwent adenosine-assisted transvenous embolization in only one transvenous session. Informed consent was obtained from all patients before intervention. The patients included had a nidus size less than 3cm, deep cerebral AVMs that are not suitable for surgical resection, and AVMs with a single or few draining veins and too small feeding arteries. We retrospectively evaluated patient demographics, neurological deficits and initial Glasgow Coma Scale (GCS). Moreover, we assessed lesion-specific characteristics including location, Spetzler–Martin (SM) grading, arterial feeders and draining veins, as well as the volume of the intracranial hemorrhage (ICH). We reviewed intraprocedural details including the total adenosine dose and the duration of cardiac arrest, as well as the need for additional open surgical treatment or repeated endovascular interventions. We evaluated the modified Rankin Scale (mRS) at discharge and at the last follow-up. The same interventional technique was used in all six patients as described in the Results.

Results

We transvenously embolized six ruptured AVMs in six patients including five males and one female. All patients presented with an ICH with an average volume of 25 ± 8 cc. At initial presentation, all patients suffered from hemiparesis, and the average GCS was 13 ± 2. All patients had SM grade 3 AVMs. Patients received an average adenosine dose of 30 ± 4 mg inducing an average cardiac arrest of 18 ± 3 seconds. There were no major procedural complications. One patient required ICH evacuation via craniotomy and one patient required an external ventricular drain. Two patients also underwent additional arterial embolization for sufficient nidus occlusion before transvenous embolization. At discharge, three patients had a mRS of 2, two patients had a mRS of 3 and one patient had an mRS of 1. At 6 months postembolization, the mRS scores were as follows: four patients had a mRS of 2 and two patients had a mRS of 1 (Table 1).

Table 1.

Patient characteristics, brain AVM grading, clinical presentation and follow-up results.

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6
Gender	Male	Male	Male	Male	Male	Female
Age	25	19	32	17	19	27
Presentation	Left hemiparesis	Right hemiparesis	left hemiparesis	Left hemiparesis	Right hemiparesis	Left hemiparesis
ICH volume	15 cc	20 cc	24cc	40 cc	27 cc	23 cc
Initial mRS	4	2	2	4	3	1
Location	Right medial frontal lobe and corpus callosum	Left basal ganglia (BG)	Right temporal	Right basal ganglia (BG)	Left temporal and insular lobes	Right BG
Nidus size	25 mm	14mm	17 mm	22 mm	25 mm	27 mm
Feeder	Right ACA (pericallosal) and right PCA (medial posterior choroidal artery)	Left anterior choroidal artery and left lenticulostriate arteries	Right lenticulostriate arteries	Right MCA (lateral lenticulostriate)	Left MCA (left lenticulostriate)	Right anterior choroidal artery and right PCA
Drainage	Deep venous system toward right ICV	Left internal cerebral vein(ICV)	Deep venous system toward right ICV	Right thalamostriate vein toward ICV	Deep venous system toward left ICV	Deep venous system toward ICV
SM grading	3	3	3	3	3	3
Additional open surgery	External ventricular drainage			Craniotomy &ICH evacuation		Gama knife 1 year before ICH
Previous endovascular embolization					Arterial embolization	Two times arterial embolization
Adenosine dose	2*35 mg	28 mg	28 mg	25 mg	30 mg	35 mg
Duration of cardiac arrest	20 seconds	15 seconds	15 seconds	15 seconds	20 seconds	20 seconds
mRS discharge	3	2	2	2	3	1
mRS6 months	2	1	2	2	2	1

ICH: intracranial hemorrhage; mRS: modified Rankin Scale; ACA: anterior choroidal artery; PCA: posterior choroidal artery; MCA: Middle cerebral artery; SM grading: Spetzler–Martin grading.

Procedure details

A right femoral artery approach was used to insert a 6 French (6F) short sheath (15 cm length). Cerebral angiography including the venous phase was performed to define the neuroanatomical features of the lesion and to create a venous roadmap for navigation. A 6F-long sheath (90 cm length) was introduced over a hydrophilic glide wire (260 cm in length) to reach to the right internal jugular vein. Then a (6F) Navien support catheter (Medtronic, Minneapolis, MN, USA) was inserted and advanced to the right straight sinus.

The main venous drainage pathway of the AVM nidus was navigated using a Marathon (Medtronic, Minneapolis, MN, USA) microcatheter over a Mirage microwire (Medtronic, Minneapolis, MN, USA). We placed the tip of microcatheter in the most proximal point of the nidus and as far distally as possible into the venous system. Superselective angiography was performed, aiming to reveal the microarchitecture of lesion and adjusting the tip of microcatheter to optimal position and determining the amount of the Onyx reflux

The embolization was done in two sequential stages; at each stage 35 mg of adenosine was quickly injected intravenously (0.5 mg/kg). The circulatory arrest with a mean arterial pressure of 40 mmHg was established for 20–30 seconds. Immediately after cardiac arrest, Onyx is injected rapidly and forcefully to form a plug in the proximal part of the nidus and vein to nidus junction; after that Onyx is ​​injected at a controlled speed to perform retrograde embolization. Casting of the nidus with the embolic material was performed from the proximal part of the nidus, occluding the access of the arterial feeders.

After completion of Onyx injection, transarterial angiography was performed to demonstrate complete occlusion of the lesion (Figure 1(a) to (c)). Another five cases of right and left basal ganglia region hemorrhagic small niduses of AVMs were embolized via transvenous approaches under adenosine-induced circulatory arrest, and Figures 2–6 reveal complete occlusion of the niduses.

Figure 1.

(a to c) Separated small deep-seated arteriovenous malformation (AVM) nidus at deep white matter of frontal lobe that was fed by fine branches derived from right anterior choroidal artery (ACA). It was drained to deep venous system toward right internal cerebral vein (ICV). Cast of Onyx deployment under adenosine-induced circulatory arrest revealed compete occlusion of nidus.

Figure 2.

(a to c) Deep-seated left frontal small hemorrhagic nidus of arteriovenous malformation (AVM) that was fed by multiple fine feeders from left medial lenticulostriate branches and drained to left internal cerebral vein (ICV). Images demonstrate transvenous Onyx cast deployment and complete occlusion of nidus.

Figure 3.

Cast of Onyx deployment and complete occlusion of right basal ganglia small hemorrhagic nidus of arteriovenous malformation (AVM) that fed by right lenticulostriate branches under adenosine circulatory arrest.

Figure 4.

Right and left basal ganglia region hemorrhagic small niduses of AVMs that were embolized via trans venous approaches under adenosine-induced circulatory arrest. Images show complete occlusion of niduses.

Figure 5.

Right and left basal ganglia region hemorrhagic small niduses of AVMs that were embolized via trans venous approaches under adenosine-induced circulatory arrest. Images show complete occlusion of niduses.

Figure 6.

Right and left basal ganglia region hemorrhagic small niduses of AVMs that were embolized via trans venous approaches under adenosine-induced circulatory arrest. Images show complete occlusion of niduses.

Case report

A 25-year-old male was admitted to the emergency department suffering from severe headache and weakness on his left side. Neurological examination showed papilledema, as well as left hemiparesis in upper and lower extremities (motor grade 4/5). Head computed tomography scan showed intracerebral hemorrhage (ICH) in the right basal ganglia (BG) with about 15 ml and intraventricular hemorrhage. After emergent placement of an external ventricular drain, the patient was taken to the angiography suite. Cerebral catheter angiography revealed a small, deep-seated AVM nidus measuring less than 3 cm in maximum diameter with an intra-nidal aneurysm in the right mesial frontal lobe at the corpus callosum. It was fed by the pericallosal segment of the right anterior cerebral artery. The veins drained to the deep venous system, which subsequently drained into the right internal cerebral vein (ICV) (Figure 1(a) to (c)).

After detailed study of the lesion characteristics including feeders, venous drainage and flow pattern, the decision for a transvenous embolization was made. However, the high flow of the lesion posed a risk for migration of embolic materials and complications. We therefore decided to perform temporary flow arrest.

Discussion

Endovascular transvenous treatment was first described in 1980 by Halbach et al. for treatment of carotid-cavernous fistulas (CCF) and dural arteriovenous fistulas (DAVF). ¹¹ This technique was later adapted for treatment of vein of Galen aneurysmal malformations. ¹²

Owing to vascular structural differences between AVMs and CCFs and DAVFs, the transvenous technique may not be applied to AVMs in the same fashion. In CCF and DAVF, the fistula exists in a layer of dura, and premature closure of the venous outflow is not necessarily associated with an increased risk of rupture or swelling.^1,13 By contrast, the transvenous method is challenging in AVMs because the arteriovenous shunt is in the brain parenchyma and the access route through the vein is usually tortuous. ¹⁴ In previous years, this method was avoided due to the concern of venous closure and arterial feeder patency and subsequently an increased risk of AVM rupture. ¹⁵

Transarterial AVM embolization is centripetal, i.e. the arterial feeders are first embolized and then the nidus occluded. Transvenous embolization, on the other hand, is centrifugal, i.e. first the nidus is occluded and then the feeders are closed in a retrograde manner. ¹⁶

In 1999, Massoud et al. were the first to introduce a transvenous approach for the endovascular treatment of AVMs. ¹⁷ In this model, systemic hypotension and balloon placement in the AVM feeders are used to reduce the pressure difference between the nidus and draining vein and to enhance the retrograde penetration of the embolic agent from the vein toward the nidus. Mendes et al. performed the largest case series in which 40 patients were treated using the transvenous method with an occlusion rate of 92%. ¹⁸ An important aspect of this method is that the venous outflow should be maintained until the nidus is completely occluded. It is critical that the transvenously introduced microcatheter remains as close to the nidus as possible before injecting embolic material. ¹⁹

Histopathological studies revealed that the venous wall is arterialized due to a higher-than-normal intraluminal pressure and becomes thicker than a normal vein, which increases the safety of the venous approach.^20,21

Relative indications for the transvenous approach include a nidus size of less than 3 cm, deep cerebral AVMs that are not suitable for surgical resection, and AVMs with a single or few draining veins and tiny feeding arteries.^1,9

In an AVM with several draining veins, embolization of a draining vein without prior nidus occlusion can increase the intranidal pressure leading to subsequent rupture and hemorrhage. ⁴ In large AVMs with multiple feeding arteries and draining veins, it seems that the transvenous approach is most effective when AVM feeders are closed first via the transarterial route. The nidus size is then reduced thereby decreasing the intranidal pressure and improving the chance of retrograde nidus occlusion. ⁹ Disadvantages of the transvenous method include the risk of pulmonary embolism due to anterograde migration of embolic material and, as mentioned above, hemorrhage following increased intranidal pressure due to premature venous closure. ²²

Inducing perioperative hypotension has proven helpful in endovascular as well as in surgical treatment of AVMs.^1,23 Several studies reported that decreased AVM flow through systemic hypotension, adenosine-induced cardiac arrest, or balloon occlusion in the AVM feeder artery, enables a more controlled injection of the embolizing agent in the transarterial method by increasing the retrograde filling of the nidus. ²⁴ One study found that occlusion of the main feeder in an AVM decreased the pressure in the draining vein by at least 50%, and complete occlusion of all feeders reduced the draining vein pressure to zero. ²⁵ Therefore, inducing local or systemic hypotension can reduce the intranidal pressure and facilitate successful nidus occlusion via the transvenous approach. ¹

Adenosine is a nucleotide analog that binds to cardiac A1 receptors and results in decreased intracellular cAMP and reduced Ca influx to the cells.^10,26 Adenosine takes effect 10-20 seconds after bolus administration inducing AV node block, bradycardia and subsequent cardiac arrest. ²⁴ With a half-life of 0.6 to 20 seconds, the effects of adenosine resolve rapidly. ²⁷

Following cardiac arrest for a few seconds, Onyx is immediately injected to form a plug at the vein to nidus junction to perform retrograde embolization. In this method, the microcatheter should be placed as close to the nidus as possible to prevent premature venous occlusion.

Some previous studies used an intravenous coil before injecting the embolic agent to increase the venous resistance and reduce the odds of Onyx reflux. This technique is referred to as the transvenous pressure cooker technique.^18,22,28,29 However, in some cases, it may prove difficult to introduce two catheters into the vein. Another method to reduce the risk of migration of the embolic material is to perform a balloon occlusion in the sinus closest to the draining vein prior to the Onyx injection. ¹⁸

In contrast to the transarterial method, the injection time should be as short as possible in the intravenous approach to enable early plug formation. The characteristics of Onyx, a non-adhesive ethylene vinyl alcohol copolymer, enables better control during injection and therefore facilitates the use of transvenous embolization.^1,29 A favorable characteristic of Onyx is its adhesion along the venous wall in concentric layers that does not immediately occlude the vein. With the decrease of the lumen diameter the forward flow of the AVM is reduced before complete nidus occlusion occurs. ²⁸

Advantages of the intravenous approach include reduced risk of ischemia compared to the transarterial method as well as higher infiltration of the embolic agent into the nidus. ¹⁸ There are several reports of the transvenous treatment of cerebral AVMs as salvage technique when other endovascular methods were not effective.^8,30 Another advantage of adenosine injection in the transvenous approach is the decreased time of intervention compared to systemic hypotension or balloon placement in the AVM feeder.

Contrary to the transarterial method, the transvenous approach can only be utilized in a specific subset of patients and is not suitable as a standard procedure for all AVM lesions. While this technique can be helpful in certain patients, the aforementioned risk factors mandate careful patient selection to ensure patient safety and favorable clinical outcomes.

Conclusion

The use of adenosine to induce a temporary circulatory arrest facilitates safe and efficient transvenous embolization of certain AVMs and was not associated with any procedural complications in our case series. However, careful patient selection is necessary, as this approach is not suitable as a standard procedure for all types of cerebral AVMs.