Risk factors and management of intraprocedural rupture during coil embolization of unruptured intracranial aneurysms: role of balloon guiding catheter

Introduction Intraprocedural rupture (IPR) is a serious complication of endovascular coil embolization of unruptured intracranial aneurysms (UIAs). Although outcomes after IPR are poor, methods to prevent subsequent neurological deterioration have not yet been investigated. We evaluated the risk factors and management strategies for IPR, particularly the role of balloon guiding catheters (BGCs) in rapid hemostasis. Methods We retrospectively reviewed all UIA cases treated with coil embolization at three institutions between 2003 and 2021, focusing on preoperative radiological data, operative details, and outcomes. Results In total, 2,172 aneurysms were treated in 2026 patients. Of these, 19 aneurysms in 19 patients (0.8%) ruptured during the procedure. Multivariate analysis revealed that aneurysms with a bleb (OR: 3.03, 95% CI: 1.21 to 7.57, p = 0.017), small neck size (OR: 0.56, 95% CI: 0.37 to 0.85, p = 0.007), and aneurysms in the posterior communicating artery (PcomA) (OR: 4.92, 95% CI: 1.19 to 20.18, p = 0.027) and anterior communicating artery (AcomA) (OR: 12.08, 95% CI: 2.99 to 48.79, p < 0.001) compared with the internal carotid artery without PcomA were significantly associated with IPR. The incidence of IPR was similar between the non-BGC and BGC groups (0.9% vs. 0.8%, p = 0.822); however, leveraging BGC was significantly associated with lower morbidity and mortality rates after IPR (0% vs. 44%, p = 0.033). Discussion The incidence of IPR was relatively low. A bleb, small aneurysm neck, and location on PcomA and AcomA are independent risk factors for IPR. The use of BGC may prevent fatal clinical deterioration and achieve better clinical outcomes in patients with IPR.

Balloon guiding catheters (BGCs) are commonly used in combination with thrombectomy catheters, such as aspiration catheters or stent retrievers, for treating acute ischemic stroke.In the setting of IPR during coil embolization of aneurysms, BGCs can achieve rapid hemostasis and may prevent fatal outcomes.At our institutions (main and two affiliated university hospitals), we have been using BGCs to treat suitable ruptured aneurysms or UIAs since 2010.
In this study, we investigated the incidence, risk factors, and outcomes of IPR at our institutions and analyzed the role of BGCs in the endovascular treatment of UIAs.To the best of our knowledge, this is the first study to address the role of BGCs in the management of IPR of UIAs.

Patients and data collection
This study was approved by the Ethics Committee of The Jikei University School of Medicine [approval number 29-228(8844)].Informed consent was obtained from the patients for all surgical procedures performed in this study.
We retrospectively reviewed all cases of saccular UIAs initially treated with coil embolization at our university hospitals between January 2003 and March 2021.Cases of mycotic, dissecting, fusiform, traumatic, and pseudoaneurysms, aneurysms related to arteriovenous malformations, dural arteriovenous fistulas, and moyamoya disease, and aneurysms treated with parent artery occlusion and flow diverters were excluded.We also excluded cases of ruptured aneurysms because of the difficulty in assessing whether neurological deterioration was due to the initial subarachnoid or intraprocedural hemorrhage.
Data collected from medical records included age; sex; medical history; family history of subarachnoid hemorrhage, UIA, or polycystic kidney disease; aneurysm size (dome and neck), location (internal carotid artery [ICA], anterior cerebral artery, middle cerebral artery, vertebrobasilar artery, or other), and presence of blebs; PHASES score (19); UCAS score (20); type of endovascular procedure (simple, double-catheter, balloon-assisted, or stent-assisted); cause of rupture (microcatheter, micro-guidewire, or coil); and type of guiding catheter (with or without balloon).Morbidity was defined as a decrease in the modified Rankin Scale score 30 days after treatment compared with the pre-treatment score.
Patients were divided into IPR and non-IPR groups on the basis of whether IPR occurred during coil embolization, as well as into BGC and non-BGC groups on the basis of whether guiding catheters with or without balloon were used.

Endovascular procedures
All endovascular procedures were performed under general anesthesia by or under the supervision of the attending physician.Patients received oral antiplatelet therapy (100 mg aspirin alone or 100 mg aspirin and 75 mg clopidogrel) before the procedure.Heparin was intravenously administered to maintain the activated clotting time at twice the normal value.Although the selection of the guiding catheter was based on the surgeon's preference, BGCs (8 or 9F, Optimo, Tokai Medical Inc., Aichi, Japan, Merci Guiding system, FlowGate, Stryker, Kalamazoo, MI, United States) were the first-line guiding catheters for all anterior circulation aneurysms.In the case of tortuous vessel anatomy, as judged by the operator, even in the anterior circulation, or in the case of posterior circulation aneurysms, non-BGCs (6-8F guiding catheter or sheath) were used.We defined balloon-assisted coiling as coil embolization during which the balloon was inflated.We always prepared the microballoon on a tray regardless of the procedure performed (with or without balloonassisted coiling).

Diagnosis and management of IPR
IPR was diagnosed by visualizing contrast extravasation.Immediately after IPR identification, the guiding catheter-mounted balloon was inflated to control bleeding.Blood pressure was decreased to normal, and protamine sulfate (30-40 mg) was administered.Additional coil placement was performed until the bleeding stopped, and cone-beam computed tomography was performed to evaluate the degree of subarachnoid hemorrhage and brain swelling.

Statistical analysis
Continuous variables are expressed as median values (interquartile range) and categorical variables as numbers (%).Statistical significance was assessed using the Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables.The association between baseline factors and IPR was analyzed using univariate and multivariate logistic regression analyses adjusted for confounding factors.Because of the extremely small number of IPR cases (n = 19) in this study, the adjustments were limited to age and sex.The association between aneurysm location and IPR was evaluated with ICA aneurysms without posterior communicating artery (PcomA) involvement as the reference.In the analysis of the association between adjunctive techniques and IPR, the simple technique was considered as the reference.In all analyses, a p-value <0.05 was considered statistically significant.All statistical analyses Abbreviations: AcomA, anterior communicating artery; BGCs, balloon guiding catheters; ICA, internal carotid artery; IPR, intraprocedural aneurysmal rupture; PcomA, posterior communicating artery; UIAs, unruptured intracranial aneurysms.3 Results

Patient characteristics
Of the 2,799 aneurysms treated in our hospitals during the study period, 2,172 UIAs in 2026 patients were included in this study (Figure 1).Table 1 summarizes the patients' demographic characteristics.There were no significant differences in medical or family histories between the IPR and non-IPR groups.BGCs were used for 1,082 aneurysms and non-BGCs for 1,090 aneurysms.

Timing and management of the IPR
As shown in Table 4, IPR occurred in 2 aneurysms during access and in 17 aneurysms during coiling.The IPR points were at the aneurysm neck (n = 1) and dome (n = 18).Thirteen ruptures were caused by the coil because of inappropriate microcatheter tip positioning or shape in the aneurysm sac, and five were caused by the microcatheter itself.One was caused by the microguidewire.
Additional surgical procedures were performed in five patients.One patient underwent hematoma evacuation, followed by clipping of the middle cerebral artery in the hybrid operating room.The patient was discharged 10 days after the procedure without any deficits.Four patients underwent ventriculostomy to control intracranial pressure.One patient died because of difficulty in controlling aneurysmal bleeding.In this case, a non-BGC was used, and an unsuccessful attempt was made to advance the microballoon across the neck of the aneurysm.In addition, because the contralateral A1 was large, balloon occlusion of the ipsilateral A1 did not result in hemostasis.
There was a significant difference in the morbidity-mortality rate after IPR between the non-BGC and BGC groups (44.4% vs. 0%, p = 0.033).None of the patients in the BGC group experienced any neurological deterioration or severe headaches.In contrast, the morbidity and mortality rates in the non-BGC group were 33% and 11%, respectively (Table 5).

Risk factors
In this study, AcomA and PcomA aneurysms were independent risk factors for IPR.Numerous previous studies have reported similar findings for AcomA aneurysms (4,6,8,10,12,16,17), including two recent studies specifically limited to UIAs in which AcomA aneurysms were identified as an independent risk factor in multivariate analyses (8,16).Aneurysms in this region are distal and tortuous, making microcatheter navigation unstable and often highly technically challenging (23).These anatomical features may reflect the difficulty of the treatment.In contrast, only one study has reported that PcomA aneurysms are statistically at risk for IPR (18).In the present study, PcomA aneurysms had the second highest incidence of intraoperative rupture after AcomA aneurysms; however, the risk may have been overestimated because PcomA aneurysms were statistically analyzed in comparison with ICA aneurysms that did not involve PcomA.As shown in the ISUIA and UCAS trials, PcomA aneurysms have a high risk of spontaneous rupture, which may be related to the high rate of IPR (24).
Irregular aneurysm morphology, including blebs, is associated with aneurysm rupture.Studies on both ruptured and unruptured aneurysms have reported that blebs are a risk factor for IPR, and the results of our study confirmed this (6,17,25,26).In the current study, a narrow aneurysm neck was also an independent risk factor for IPR.This is the first time a study of UIAs has found a narrow neck to be a risk factor.Although similar findings have been reported for ruptured cerebral aneurysms (13), other studies have reported a wide neck as a risk factor (5). Aneurysms with narrow necks restrict catheter movement and may result in direct pressure on the aneurysmal wall owing to the coil.Although small aneurysm size was not found to be a significant risk factor in this study, several prior studies have reported contrasting results, and the reason may be the same as that for narrow aneurysm neck (6,(8)(9)(10)17).

Role of BGCs
Although no significant difference was observed in the incidence of IPR between the BGC and non-BGC groups, the use of BGCs was associated with good clinical outcomes, without recorded cases of morbidity or mortality.The microballoon was prepared on a tray in all cases with or without balloon-assisted coiling; however, it took longer to guide the microballoon to the aneurysm neck during IPR in cases without balloon-assisted coiling.Therefore, BCGs may have achieved an early hemostatic effect.In addition, no complications, such as vessel dissection or hemodynamic infarction, were observed with the use of BGCs.
BGCs have been widely used following reports on their benefits in mechanical thrombectomy (27).The device is now considered the standard guiding system for thrombectomy in many centers to avoid trapped thrombus migration.Although the use of BGCs is widely accepted in neurointerventional procedures, this guiding system is not commonly used to treat cerebral aneurysms.We used an 8F BGC for flow control in cases of aneurysm IPR.The balloon can be inflated immediately, and flow control can be achieved within seconds.Using   proximal flow control, additional coils can be advanced into the aneurysm until the bleeding site is completely occluded.The balloon is typically deflated after 2-3 coils are placed to assess angiographic hemostasis.In most cases, hemostasis was achieved within 5 min.Subarachnoid hemorrhage in this group was usually minimal, and follow-up computed tomography scans the following day showed blood washout in most cases (Figure 2).Overall, the system is simple, does not require additional techniques, and allows for immediate control of bleeding.A disadvantage is that the system is not suitable for posterior circulation or tortuous ICA aneurysms because of the size of the existing balloon guiding systems.

Limitations
This study has several limitations.First, the retrospective study design may have introduced selection bias and affected the generalizability of our findings.Second, the number of patients with IPR was small, which may have limited the statistical power to detect significant differences between the groups.Furthermore, given the small number of IPR cases, the effect of several measured and unmeasured confounders was not assessed in this study.Third, this was an exploratory study to identify potential risk factors for IPR in UIAs.Further research is required to assess the validity of our findings.Finally, historical improvements in antiplatelet management, mechanical devices, and surgical techniques may have had a positive effect on the results of this study.

Conclusion
Aneurysms located in AcomA and PcomA, as well as aneurysms with blebs and small necks were identified as risk factors for IPR.Our results showed that BGCs may prevent serious clinical deterioration after IPR during coil embolization.

FIGURE 2
FIGURE 2 Representative pre-and postprocedural images.(A) Three-dimensional and (B) digital subtraction angiography (DSA) images showing an unruptured anterior communicating aneurysm.(C) DSA image showing active contrast extravasation due to aneurysm perforation.(D) Angiography image showing proximal flow control with balloon guiding catheter during intraprocedural rupture.(E) Inflated balloon guiding catheter (Flowgate2; Stryker, United States).(F) Magnetic resonance image (axial view) showing no subarachnoid bleeding in the basal cistern 1 day after perforation.

TABLE 1
Patient characteristics.
IPR: intraprocedural rupture, SAH: subarachnoid hemorrhage, PKD: polycystic kidney disease, UIA: unruptured intracranial aneurysm.Continuous variables are presented as medians (interquartile ranges), while categorical variables are presented as numbers (%).p-values were calculated using Wilcoxon's rank-sum test for continuous variables and Fisher's exact test for categorical variables.

TABLE 3
Univariate and multivariate logistic regression analyses adjusted for age and sex.

TABLE 2
Morphological and surgical characteristics.

TABLE 5
Outcomes related to balloon guide catheter use.: balloon guide catheter, IPR: intraprocedural rupture.Morbidity was defined as a decrease in the modified Rankin scale score 30 days after treatment compared to the pretreatment score.p-values were calculated using Fisher's exact test.Statistical significance was set at a two-tailed p value < 0.05. BGC