Risk factors of recurrence after endovascular embolization of posterior communicating artery aneurysms

Abstract

Background and objective

To determine the risk factors for recurrence after endovascular embolization of posterior communicating artery aneurysms (PcomA).

Methods

We retrospectively analyzed a cohort of 163 patients harboring 172 PocmAs who were treated with endovascular embolization from January 2019 to December 2020. The patients were divided into recurrence and stable groups depending on outcome. Univariate and logistic regression analyses were performed to determine the potential risk factors of recurrence during follow-up.

Results

Of the total 163 patients harboring 172 aneurysms, 107 were treated with simple coil occlusion and 65 were treated with stent-assisted coil embolization. There were significant differences in aneurysm sizes and use of non-stent-assisted coil embolizations between the groups (P < 0.05). The incidence of saccular aneurysm and Raymond grade were significantly higher in the recurrent group than in the stable group (P < 0.01). After variable selection, Raymond grade, aneurysm size, saccular aneurysm and non-stent-assisted coil embolization were included in further analysis. Binary logistic regression analysis revealed significant associations with non-stent-assisted coil embolization (P = 0.007), packing density (P < 0.001) and Raymond grades II (P < 0.001) and III (P = 0.002).

Conclusion

Non-stent-assisted coil embolization, as well as packing density and Raymond grades II grade III are associated with recurrence after endovascular treatment of PcomA.

Keywords

Posterior communicating artery aneurysm embolization endovascular treatment recurrence risk factors

Introduction

Posterior communicating artery aneurysm (PcomA) occurs in approximately 25% of all patients with aneurysms.¹ Currently, the treatment for PcomA involves microsurgical clipping. With the development of novel devices and minimally invasive surgery, endovascular treatment has become important for the treatment of intracranial aneurysms. Despite the fact that endovascular therapy has improved patient outcomes and has produced lower mortality than microsurgical clipping, the postoperative recurrence rate of 30% remains a difficult problem.² A number of studies have determined that the size of aneurysm, occurrence of rupture, Hunt-Hess grade, packing density, saccular aneurysm, and presence of stent often affect long-term stability post-embolization^.3–5 Nevertheless, the risk factors for PcomA recurrence post-embolization remain unclear. This single-center retrospective review was designed to determine potential risk factors for recurrence of PcomA.

Materials and methods

Study participants were recruited from the Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College. The study was performed in accordance with the Declaration of Helsinki. This study was approved by our Institutional Review Board, which waived the requirement for written informed consent.

Patients and aneurysm characteristics

From January 2019 to December 2020, we enrolled 193 patients (209 PcomAs) who underwent endovascular embolization. The study end point was the timing of recanalization during follow-up, 30 patients were excluded (16 cases with 20 aneurysms were lost follow-up, 8 cases with 10 aneurysms were vegetative states and 6 cases with 7 aneurysms were deaths). Ultimately, 163 patients with 172 aneurysms and met inclusion criteria. As shown in Figure 1. Inclusion criteria were as follows: (1) diagnosis of PcomA using angiography; (2) complete clinical history data and follow-up more than 6 months. Exclusion criteria were as follows: (1) no PcomA; (2) lack of completed clinical history data or loss to follow-up; and (3) non-endovascular treatment. Morphological data were obtained using digital subtraction angiography (DSA). Aneurysm size was categorized as small (<7 mm) or large (≥7 mm) according to previous experience.⁶ An aneurysm was considered to have a wide neck if its size was ≥4 mm and/or if the D/R (dome-to-neck ratio) was <2.⁷ On admission, patients with Hunt-Hess grades of 0–3 were classified as lower grade, and those with Hunt-Hess grades of 4–5 score were classified as high grade.^8,9 Computerized tomography (CT) findings suggestive of subarachnoid hemorrhage or detection by lumbar puncture of hemorrhagic cerebrospinal fluid defined ruptured aneurysms. Abnormal protrusions in the aneurysm wall are defined as saccular aneurysms. Those aneurysms appeared again while complete occlusion after 3 month and/or residual aneurysm size had increased after incomplete occlusion were regard as recurrent aneurysm.¹⁰

Figure 1.

Flow chart shows overall study process.

Endovascular procedure and pharmacologic therapy

All patients were operated on under general anesthesia and received heparin intra-operatively (80 U/kg) to maintain activated clotting times 2–3 times the baseline value. A 6-F guiding catheter was introduced through a femoral sheath into the carotid artery. All procedures were performed on a biplane angiographic system. Whether we performed simple occlusion or stent-assisted occlusion depended on the characteristics of aneurysm. All operations were conducted strictly according to the manufacturer's instructions. Cosmos, helical and complex coils (all from MicroVention Co., US) were used for simple occlusion. Enterprise (Cordis Co., US), LVIS (MicroVention Co.) and Solitaire stents (Ev3 Co., US) were used for stent-assisted occlusion.

Patients with unruptured aneurysms who required stent-assisted coil embolization were medicated with dual antiplatelet therapy 3–5 days prior to stent deployment (aspirin 100 mg/d + clopidogrel 75 mg/d). For those with ruptured aneurysms, aspirin and clopidogrel (each 300 mg) were administered orally or per rectum 2 h before stent deployment. All patients were subsequently treated with aspirin 100 mg and clopidogrel 75 mg daily for 6 weeks, followed by aspirin only indefinitely. No antiplatelet drugs were taken before or after embolization for simple occlusions.

Angiographic follow-up

DSA was used to measure the degree of aneurysm embolization immediately postoperatively. Mean angiographic follow-up was 11.4 ± 3.9 months (median, 11 months; range 6–24 months). The results were assessed by at least two neurosurgeons. The immediate postoperative angiogram and follow-up images were studied to assess the degree of aneurysm occlusion using the Raymond–Roy Grade Scale (RRGS)^11,12: Complete occlusion was considered Raymond grade I, residual neck was considered Raymond grade II and dome filling was defined as Raymond grade III.

Statistical analysis

All data were analyzed using SPSS Statistics version 20.0 (SPSS, Inc., Chicago, Illinois, USA). Data were presented as mean ± standard deviation (SD). Pearson chi-square test or Fisher's exact test were used to evaluate categorical variables and Student t-test or Mann-Whitney U test for continuous variables. As predetermined, variables with P-values <0.05 in the univariate analysis were included in the binary logistic regression analysis. P < 0.05 was considered statistically significant.

Results

Baseline characteristic of patients with PcomA

A total of 172 PcomA in 163 patients completed the follow-up. Patient characteristics are summarized in Table 1. The cohort consisted of 67 males and 105 females, with a median age of 53 years (range 21–87 years). The numbers of patients who had a medical history of hypertension, diabetes mellitus were 59 (34.3%) and 48 (27.9%), respectively. Fifty-seven (33.1%) were former or current smokers. There were no significant differences in gender, age, hypertension, smoking and diabetes between the groups (P > 0.05; Table 1).

Table 1.

Baseline characteristics of the patients with posterior communicating artery aneurysms.

Baseline characteristics	Recurrence group (n = 45, %)	Stable group (n = 127, %)	P-value
Gender			0.586
Male	16 (35.6)	51 (40.2)
Female	29 (64.4)	76 (59.8)
Age (Years)			0.779
≥53	23 (51.1)	68 (53.5)
<53	22 (48.9)	59 (46.5)
Smoking			0.879
Yes	14 (31.1)	43 (33.9)
No	31 (68.9)	84 (66.1)
Hypertension			0.451
Yes	18 (40.0)	41 (32.3)
No	27 (60.0)	86 (67.7)
Diabetes			0.127
Yes	17 (37.8)	31 (24.4)
No	28 (62.2)	96 (75.6)

The median age was 53 years.

Characteristics of PcomA between recurrence and stable groups

After univariate analysis between two groups, we found that aneurysm size (P = 0.046), neck size (P = 0.013), Raymond grade occlusion classification (P < 0.001), saccular aneurysm (P = 0.007), packing density (P < 0.001) and non-stent assisted coil embolization (P = 0.032) were significantly associated with recurrence. These confounders were corrected for using logistical regression analysis (Table 2).

Table 2.

Characteristics of posterior communicating artery aneurysms.

Aneurysm characteristic	Recurrence group (n = 45, %)	Stable group (n = 127, %)	P-value
Rupture			0.690
Yes	35 (77.8)	95 (74.8)
No	10 (22.2)	32 (25.2)
Saccular			0.007
Yes	18 (40.0)	25 (19.7)
No	27 (60.0)	102 (80.3)
Non-stent assisted			0.032
Yes	34 (75.6)	73 (57.5)
No	11 (24.4)	54 (42.5)
Single aneurysm			0.282
Yes	31 (68.9)	76 (59.8)
No	14 (31.1)	51 (40.2)
Aneurysm grade			0.147
High	14 (31.1)	26 (20.5)
Low	31 (68.9)	101 (79.5)
Neck size
≥4 mm	19 (42.2)	29 (22.8)	0.013
<4 mm	26 (57.8)	98 (77.2)
Packing density			<0.001
≥20%	11 (24.4)	94 (74.0)
<20%	34 (75.6)	33 (26.0)
Size			0.046
≥7 mm	19 (42.2)	31 (24.4)
<7 mm	26 (57.8)	96 (75.6)
Raymond grade			<0.001
I	19 (42.2)	101 (79.5)
II	16 (35.6)	24 (18.9)
III	10 (22.2)	2 (1.6)

Logistic regression analysis of aneurysm recurrence post-embolization

Stent-assisted coil embolization, packing density and Raymond grade were independent variables. Aneurysm recurrence post-embolization was the dependent variable. Significant variables in the univariate analysis were entered in binary logistic regression analysis. After logistic regression analysis, there were significant associations with non-stent-assisted coil embolization, as well as packing density and Raymond grades II and III (all P < 0.05; Table 3).

Table 3.

Logistic regression model assessing risk of recanalization in posterior communicating artery aneurysms.

Variables	B	Odds ratio	95% Confidence interval	P-value
Raymond grade I	Ref	Ref	Ref	—
Raymond grade II	5.273	194.952	16.803–2261.836	<0.001
Raymond grade III	3.959	52.388	4.039–679.565	0.002
Non-stent-assisted	1.865	6.459	1.646–25.346	0.007
Packing density	2.555	12.873	3.232–51.272	<0.001

Ref: Reference.

Discussion

With improved perioperative outcomes and trends toward minimally invasive surgery, endovascular treatment for intracranial aneurysm have become increasingly popular.^13,14 Despite this surge in popularity and studies showing good results, increasing numbers of surgeons have questioned the long-term efficacy of endovascular treatment for aneurysms. The purpose of our study was to determine the potential risk factors for recurrence of PcomA.

Aneurysm size influences the incidence of recurrence of aneurysms post-embolization. Some studies^11,15 showed that aneurysm size >10 mm was an important factor for recurrence, and the incidence of recanalization post-occlusion would increase 0.12% for every 1% increase in diameter. Park et al.¹⁶ reported that aneurysm size ≥8 mm was an independent risk factor for recurrence after endovascular treatment. A similar study⁶ of 400 paraclinoid aneurysms managed with endovascular treatment reported that aneurysms ≥7 mm had a higher incidence of rupture and recurrence. In a study of 870 saccular aneurysms,¹⁷ aneurysms ≤7 mm were more susceptible to late recanalization (more than 6 months). By contrast, early recanalization (within 6 months) correlated with size >7 mm, while aneurysms ranging from 4 to 7 mm were more prone to delayed recanalization. Murayama et al.¹⁸ reported a 5.1% overall recanalization rate for small aneurysms (4–10 mm), which was much lower than the 35.3% rate for larger aneurysms. In the present study, we showed that aneurysm size correlated with recurrence after occlusion (P < 0.001), a similar result. Nevertheless, size was not an independent risk factor for recanalization. Furthermore, we found that saccular aneurysms had a recurrence rate of 40.0%, higher than rates reported in other studies. The reason for higher rate may be that, in irregular aneurysms, it was difficult to achieve complete embolization, and therefore it was difficult to generate thrombosis in the aneurysmal sac.

Stent-assisted coil embolization for intracranial aneurysms is another putative factor for aneurysm recanalization. Stents are increasingly used in this setting while aneurysms with wide necks require greater coil packing and flow diversion. Recurrence rates registered after simple coil embolization were significantly higher than those encountered after stent-assisted coil embolization.^19–21 Piotin et al.²² reported that the incidence of recanalization after embolization with stent-assisted coils (14.9%) were notably lower than those after simple coil embolizations (33.5%). A similar study²³ of 114 small PcomA (3–10 mm) reported that the rate of recanalization in the stent group (4.4%) was significantly lower than that of the non-stent assisted group (30.2%). These results suggested that the use of stents may alter the hemodynamics in the aneurysm, improving the packing density and promoting the proliferation of intravascular membrane.^24,25 The present study demonstrated that non-stent-assisted coil embolization was an independent risk factor for recanalization (P < 0.01), consistent with results of previous studies.

Packing density is another important factor for recurrence post-embolization. Raymond et al.²⁶ reported that incomplete occlusion during treatment of aneurysms with coils was a risk factor for aneurysm recanalization. Linzey et al.²⁷ studied 122 stent-assisted coil aneurysms and concluded that aneurysms with <20% packing density were more likely to have clinically significant recurrences than those with >20% packing density, and the required reoperation rates were 19% and 5.1%, respectively. Lawson et al.²⁸ reported that packing density was a predictor of complete occlusion in aneurysms treated with stent-assisted coil embolization. A study of 49 circumferential unruptured aneurysms⁴ also found that packing density was the main predictor of complete occlusion and aneurysm recurrence. In the present study, packing density not only was a risk factor for recurrence; Raymond grades II and III were also independent risk factors for recurrence (all P < 0.01).

Smoking is a debate factor for the recurrence of aneurysms post coil embolization. Shimizu et al.²⁹ analyzed more than 400 paraclinoid aneurysms and concluded that smoking status was not an parameter of the recurrence of aneurysms post embolization. Similar in present study, the relationship between smoking status and aneurysm recurrence is not obvious. However, there are other researchers oppose views on the relationship between smoking history and aneurysm recurrence. Ortiz et al.³⁰ retrospectively more than 100 smokers and demonstrated that the rate of recurrence and recanalization of cerebral aneurysms treated with coil-embolization higher than those nonsmokers. Futchko et al.³¹ stratified their patient cohort into 3 groups with respect to smoking status—current smokers, former smokers, and nonsmokers. Their study found that a history of smoking (either current or former) was significantly and independently related to an increased risk of aneurysm recurrence after endovascular treatment. Similar research³² about three groups smoking status showed that former smokers, like current smokers, have odds of aneurysm recurrence similar to nonsmokers. The accounts for different studies finding may be the difference in the adjunctive devices used. Different therapy ways like balloon-assisted coiling or stent-assisted coiling may reach discrepancy in outcomes. In addition, short follow-up time and not enough patients may draw different outcomes. In a word, the role of smoking plays in the recurrence of aneurysms post embolization need larger populations, longer follow-up time and similar therapy way to demonstrate.

There are several limitations in our study. First, the study was designed as a retrospective review based on a single-center experience with a small sample size. Further studies with larger populations and more centers are needed to confirm our results. Second, the angiographic follow-up time was short (11.4 months). Longer angiographic follow-up times may alter the rate of progression of occlusion. Finally, we found that rupture was not a risk factor for recurrence. Nevertheless, Zuo et al.³³ and Raper et al.³⁴ demonstrated that ruptured aneurysms were strongly predictive of aneurysm recurrence. The discrepancy may be the result of the small sample size in our study. Further research with larger numbers of patients will are necessary to address this issue.

Conclusions

Non-stent-assisted coil embolization, packing density and Raymond grades II and III are risk factors for recurrence after endovascular treatment of PcomA. This suggests that neurosurgeons may need to adjust treatment of aneurysms, depending on the Raymond grade. More detailed investigations regarding lowering the rate of recanalization of PcomA are needed.

Footnotes

Authors’ contribution

DG contributed the conception, design, data analysis. XG collected the data and drafted the manuscript. BS and ZB did the conception, design, and final approval of the version to be published.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

This work was supported by the Scientific Research Project of Anhui Provincial Health Commission (no. AHWJ2021b114) and the Key Programs of Wannan Medical College (no. WK2020ZF07).

ORCID iD

Bin Sheng

References

Clajus

Sychra

Strasilla

, et al. Stent-assisted coil embolization of intracranial aneurysms using the solitaire AB neurovascular remodeling device: initial and midterm follow-up results. Neuroradiology 2013; 55: 629–638.

Gandhi

Quinn

, et al. True aneurysms of the posterior communicating artery: a systematic review and meta-analysis of individual patient data. World Neurosurg 2011; 75: 64–72; discussion 49.

Costa

Vaz

Finet

, et al. Recanalization and rupture after intracranial aneurysm treatment. J Neurosurg Sci 2019; 63: 518–524.

Tosello

Batista

Pereira

BJA

, et al. Packing density necessary to reach a high complete occlusion rate in circumferential unruptured intracranial aneurysms treated with stent-assisted coil embolization. AJNR Am J Neuroradiol 2017; 38: 1973–1977.

Chalouhi

Starke

Koltz

, et al. Stent-assisted coiling versus balloon remodeling of wide-neck aneurysms: comparison of angiographic outcomes. AJNR Am J Neuroradiol 2013; 34: 1987–1992.

Shimizu

Imamura

Mineharu

, et al. Endovascular treatment of unruptured paraclinoid aneurysms: single-center experience with 400 cases and literature review. AJNR Am J Neuroradiol 2016; 37: 679–685.

Wang

Vargas

Spiotta

, et al. Stent-assisted coiling of cerebral aneurysms: a single-center clinical and angiographic analysis. J Neurointerv Surg 2018; 10: 687–692.

Report of world federation of neurological surgeons committee on a universal subarachnoid hemorrhage grading scale. J Neurosurg 1988; 68: 985–986.

Sano

Satoh

Murayama

, et al. Modified world federation of neurosurgical societies subarachnoid hemorrhage grading system. World Neurosurg 2015; 83: 801–807.

10.

Kim MJ

Park

, et al. Recurrence and risk factors of posterior communicating artery aneurysms after endovascular treatment. Acta Neurochir 2021; 163: 2319–2326.

11.

Raymond

Guilbert

Weill

, et al. Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke 2003; 34: 1398–1403.

12.

Roy

Milot

Raymond

. Endovascular treatment of unruptured aneurysms. Stroke 2001; 32: 1998–2004.

13.

Wiebers

Whisnant

Huston 3rd

, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003; 362: 103–110.

14.

Alshekhlee

Mehta

Edgell

, et al. Hospital mortality and complications of electively clipped or coiled unruptured intracranial aneurysm. Stroke 2010; 41: 1471–1476.

15.

Ferns

Sprengers

van Rooij

, et al. Coiling of intracranial aneurysms: a systematic review on initial occlusion and reopening and retreatment rates. Stroke 2009; 40: e523–e529.

16.

Park

Bae

Cho

, et al. Risk factors for recurrence and retreatment after endovascular treatment of intracranial saccular aneurysm larger than 8 mm. Acta Neurochir 2019; 161: 939–946.

17.

Jeon

Cho

Yoo

, et al. Risk factor analysis of recanalization timing in coiled aneurysms: early versus late recanalization. AJNR Am J Neuroradiol 2017; 38: 1765–1770.

18.

Murayama

Nien

Duckwiler

, et al. Guglielmi detachable coil embolization of cerebral aneurysms: 11 years’ experience. J Neurosurg 2003; 98: 959–966.

19.

Hwang

Bang

, et al. Endovascular enterprise stent-assisted coil embolization for wide-necked unruptured intracranial aneurysms. J Clin Neurosci 2013; 20: 1276–1279.

20.

Kwon

. Endovascular coil embolization of unruptured intracranial aneurysms: a Korean multicenter study. Acta Neurochir 2014; 156: 847–854.

21.

Jeon

Cho

Rhim

, et al. Fate of coiled aneurysms with Minor recanalization at 6 months: rate of progression to further recanalization and related risk factors. AJNR Am J Neuroradiol 2016; 37: 1490–1495.

22.

Piotin

Blanc

Spelle

, et al. Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 2010; 41: 110–115.

23.

Yao

Yang

, et al. Safety and long-term efficacy of endovascular treatment of small posterior communicating artery aneurysms by coiling with or without stent: a single center retrospective study. Clin Neurol Neurosurg 2013; 115: 2502–2507.

24.

Nishido

Piotin

Bartolini

, et al. Analysis of complications and recurrences of aneurysm coiling with special emphasis on the stent-assisted technique. AJNR Am J Neuroradiol 2014; 35: 339–344.

25.

Geyik

Yavuz

Yurttutan

, et al. Stent-assisted coiling in endovascular treatment of 500 consecutive cerebral aneurysms with long-term follow-up. AJNR Am J Neuroradiol 2013; 34: 2157–2162.

26.

Raymond

Roy

. Safety and efficacy of endovascular treatment of acutely ruptured aneurysms. Neurosurgery 1997; 41: 1235–1245; discussion 1245–6.

27.

Linzey

Griauzde

Guan

, et al. Stent-assisted coiling of cerebrovascular aneurysms: experience at a large tertiary care center with a focus on predictors of recurrence. J Neurointerv Surg 2017; 9: 1081–1085.

28.

Lawson

Newman

Chi

, et al. Stent-associated flow remodeling causes further occlusion of incompletely coiled aneurysms. Neurosurgery 2011; 69: 598–603; discussion 603–4.

29.

Wang

, et al. Risk factors to predict neurologic complications after endovascular treatment of unruptured paraclinoid aneurysms. World Neurosurg 2017; 104: 89–94.

30.

Ortiz

Stefanski

Rosenwasser

, et al. Cigarette smoking as a risk factor for recurrence of aneurysms treated by endovascular occlusion. J Neurosurg 2008; 108: 672–675.

31.

Futchko

Starr

Lau

, et al. Influence of smoking on aneurysm recurrence after endovascular treatment of cerebrovascular aneurysms. J Neurosurg 2018; 128: 992–998.

32.

Brinjikji

Lingineni

, et al. Smoking is not associated with recurrence and retreatment of intracranial aneurysms after endovascular coiling. J Neurosurg 2015; 122: 95–100.

33.

Zuo

Yang

, et al. Safety of coiling with stent placement for the treatment of ruptured wide-necked intracranial aneurysms: a contemporary cohort study in a high-volume center after improvement of skills and strategy. J Neurosurg 2018; 131: 435–441.

34.

Raper

Allan

. International subarachnoid trial in the long run: critical evaluation of the long-term follow-up data from the ISAT trial of clipping vs coiling for ruptured intracranial aneurysms. Neurosurgery 2010; 66: 1166–1169; discussion 1169.