Identifying Recurrence Risk Factors in Vertebral Artery Dissecting Aneurysms Post-Intervention

doi:10.21203/rs.3.rs-5103493/v1

Background

In the realm of neurovascular disorders, vertebral artery dissecting aneurysms (VADA) stand out due to their significant morbidity and mortality rates, particularly when they lead to subarachnoid hemorrhage (SAH). Despite advancements in interventional therapies, the recurrence of VADA post-treatment remains a critical challenge, with a reported recurrence rate of 13%-25.7%. This study aims to bridge the gap in understanding the risk factors contributing to VADA recurrence after interventional therapy, a domain that has seen limited exploration.

Method

Employing a retrospective analysis, we reviewed the medical records of 64 patients diagnosed with VADA and treated with interventional therapy from 2015 to 2024. Patients were categorized based on the presence of SAH, the relationship of VADA to the posterior inferior cerebellar artery (PICA), and the type of interventional therapy received. Statistical analyses, including univariate and multivariate logistic regression, were utilized to identify factors associated with VADA recurrence.

Result

Our findings reveal that VADA located on the dominant side and the length of the dissection in the artery significantly increased the risk of recurrence. Moreover, the type of interventional therapy, specifically the use of engraving laser stent-assisted coil (SAC-L), was associated with higher recurrence rates compared to other methods. The complete occlusion rate was notably higher in patients treated with regular braided stent-assisted coil (SAC-B) and parent artery occlusion (PAO).

Conclusion

This study underscores the importance of considering the anatomical location of VADA and the choice of interventional therapy in mitigating the risk of recurrence. Our analysis provides critical insights into the factors influencing VADA recurrence, offering a valuable resource for clinicians in tailoring treatment strategies to improve patient outcomes.

Intracranial aneurysms

Vertebral artery dissection aneurysm

Interventional therapy

Recurrence

Intracranial aneurysms are surprisingly prevalent, with population studies indicating that around 3% of the general population may have these lesions[1]. The rupture of an intracranial aneurysm leading to subarachnoid hemorrhage (SAH) results in significant morbidity, high mortality rates, and a substantial healthcare burden[2, 3]. Vertebral artery dissecting aneurysms (VADA) represent the most common form of spontaneous cerebral dissection and have become a prominent cause of subarachnoid hemorrhage, particularly among young to middle-aged adults[4, 5]. Once a VADA develops, interventional therapy is required. However, research has shown that the recurrence rate of VADA following interventional therapy stands at 13%-25.7%[6, 7]. Understanding the key factors that influence VADA recurrence is crucial for reducing the recurrence rate in future VADA treatments. Therefore, this study aims to identify the risk factors associated with the recurrence of VADA after interventional treatment.

Patients:

A comprehensive review was conducted on all inpatients who underwent interventional therapy between 2015 and 2024. Patients with extracranial VADA or other dissection aneurysms were excluded from the study. Ultimately, data was collected from a total of 63 patients. This study has been approved by the Ethics Committee of Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology.

A complete review of the medical history data of all enrolled patients was conducted, including patients’ basic information (age, gender, smoking history and drinking history), chronic history (hypertension, hyperlipemia), CT (Computed tomography), integrating magnetic resonance imaging (MRI) and digital subtraction angiography (DSA), surgical information, and following outcomes. The diagnosis of dissection aneurysms was established through the utilization of a multimodal imaging approach, MRI and DSA.

FIG. 1. Types of VADA classified by PICA origin location.

FIG. 2. DSA manifestations of VADA recurrence: A. Postoperative immediate DSA; B. One-year post-surgery DSA.

Patient Grouping:

The patients were assigned to the SAH or no-SAH groups based on the results of the preoperative CT scans. The relative position of the VADA and the origin of the posterior inferior cerebellar artery (PICA) are of significant importance in determining the most appropriate surgical strategy. Therefore, according to the origin of PICA, we divided the VADAs into two subtypes: PICA or Others. The subtypes were determined by DSA (Figure 1). In order to facilitate comparison of the radiological outcomes obtained using digital subtraction angiography (DSA), the interventional therapies were divided into three groups according to the therapeutic mechanism involved: parent artery occlusion (PAO), engraving laser stent-assisted coil (SAC-L) and regular braided stent-assisted coil (SAC-B).

Table1 Comparison of baseline data, radiological features, therapies, and SAH

Variable	NO. of Patients	SAH	non-SAH	p value
Gender, n (%)				0.084
male	51(80.9)	9(69.2)	42(84.0)
female	12(19.1)	4(30.8)	8(16.0)
Age, n (%)				0.315
≥55 years old	30(47.6)	4(30.8)	26(52.0)
<55 years old	33(52.4)	9(69.2)	24(48.0)
Drinking History, n (%)				0.087
Yes	21(33.3)	5(38.5)	16(32.0)
No	42(66.7)	8(61.5)	34(68.0)
Smoking History, n (%)				0.207
Yes	18(28.6)	5(38.5)	13(26.0)
No	45(71.4)	8(61.5)	37(74.0)
Hypertension, n (%)				0.297
Yes	34(54.0)	5(38.5)	29(58.0)
No	29(46.0)	8(61.5)	21(42.0)
Hyperlipemia, n (%)				0.103
Yes	19(30.2)	3(23.1)	16(32.0)
No	44(69.8)	10(76.9)	34(68.0)
Types, n (%)				0.067
PICA	20(31.7)	1(7.7)	19(38.0)
Others	43(68.3)	12(92.3)	31(62.0)
VADA with saccular structure, n (%)				0.168
Yes	41(65.1)	8(61.5)	33(66.0)
No	22(34.9)	5(38.5)	17(34.0)
VADA in dominant side, n (%)				0.233
Yes	36(57.1)	5(38.5)	31(62.0)
No	27(42.9)	8(61.5)	19(38.0)
The length of the dissection in artery	-	9.04±3.29	12.31±5.23	0.038
Intervention therapy, n (%)				0.233
SAC-L	24(38.1)	5(38.5)	19(38.0)
SAC-B	30(47.6)	2(15.4)	28(56.0)
PAO	9(14.3)	6(46.1)	3(6.0)

Abbreviations: SAH, subarachnoid hemorrhage; PICA, posteroinferior cerebellar artery; VADA, vertebral artery dissecting aneurysms; SAC-L, engraving laser stent-assisted coil; SAC-B, regular braided stent-assisted coil; PAO, parent artery occlusion.

Interventional therapy:

In total, five interventional surgical options were available for the administration of vasodilatory acetaminophen therapy (VADA). PAO entailed the direct occlusion of the VADA and its parent artery through the use of coils. In the SAC-L or SAC-B, we coiled the aneurysms with the assistance of laser engraving stent or regular braided stent. In the context of FD implantation, the procedure involved the implantation of either a Pipeline Embolization Device (PED; Medtronic Neurovascular) or a Tubridge device (MicroPort Medical). In cases where a single stent was implanted, one of two options was employed: either a regular braided stent, or a laser-engraved stent. The FD implantation and the single-stent implantation were not included in the study because of the scarcity of cases.

Follow-Up Evaluation:

All patients were hospitalized for DSA review one year after interventional therapy. Complete occlusion precluded the ability to detect VADAs on radiological review. In the case of incomplete occlusion, the VADA exhibited no appreciable change compared to its preoperative status, yet the volume had diminished (Figure 2).

Statistical Analysis:

For the purpose of making comparisons between the baseline covariates associated with SAH and those associated with non-SAH, Fisher’s exact test or Pearson’s chi-square test was employed for the analysis of categorical covariates. A univariate logistic model with a binary outcome (SAH vs. non-SAH) was employed to derive the odds ratio (OR) and the p-value, along with its corresponding 95% confidence interval (CI). In order to investigate the potential influence of covariates on outcomes, univariate logistic regression was initially applied to the comparison of complete and incomplete occlusion. Subsequently, any covariates exhibiting a p-value of less than 0.1 in the univariate model or representing clinical relevance were then incorporated into the multivariate model. All analyses were performed using R software (version 4.4.1). All p-values were two-sided, and a p-value of less than 0.1 was considered statistically significant.

Clinical Characteristics:

The series comprised a total of 63 patients. A significantly higher proportion of men than women suffer from VADA (80.9% vs. 19.1%). The mean age of all participants was 52.9 ± 11.6 years (9-74 years). SAH represents 20.6% of all patients.

Radiological Characteristics:

A total of 63 patients were examined, and 36 aneurysms were identified on the dominant side, while 27 aneurysms were observed on the non-dominant side. According to the relationship of the PICA and VADA, there were 20 PICA types and 43 other types including distal, proximal and obliteration types (Figure 1). 44 VADAs showed saccular structure. The mean length of the dissection in artery was 11.6±5.1 (3.7-31.8) mm.

Treatment:

In our study, three interventional operation choices were made for VADA treatment in total. There were 24(38.1%) SAC embolization with engraving laser stent, 30(47.6%) SAC embolization with regular braided stent and 9(14.3%) PAOs. According to the SAH in the CT scans, we analyzed the operation strategies. In SAH patients, the PAO was the most common surgical procedure we have used. In non-SAH patients, we rarely think about PAO, SAC-L or SAC-B is the common surgical procedure. Whether the VADA is located on the dominant side is also an important factor in determining the surgical plan. The PAO is rarely used in patients with SAH of VADA in dominant side, SAC reconstruction is more effective.

Follow-up Outcomes in Radiology:

The follow-up visit is scheduled for one year after the surgery. All patients were hospitalized for DSA review. The contributing factors of VADA recurrence after intervention therapy is shown on Table2. VADA in dominant side, the length of the dissection in artery and SAC-L were three contributing factors for VADA recurrence.

All VADAs were completely occluded after PAO. The complete occlusion rate was 66.7% in the SAC-L group and 80% in the SAC-B group (Figure 3). The incomplete occlusion rate of patients whose VADA is in dominant side was higher than not (33.3% vs. 7.4%). The mean of the length of the dissection in artery was different between the complete occlusion (10.6±3.7) and the incomplete occlusion (15.2±7.4).

Table2 The Contributing Factors of VADA Recurrence after Intervention Therapy by Two Factor Logistic Regression Analysis

Variable	p value	OR (95% CI)
Gender, male	0.664	0.552 (0.038-8.05)
Age	0.646	1.546 (0.241-9.932)
Drinking History	0.51	2.22 (0.206-23.877)
Smoking History	0.965	0.95 (0.098-9.195)
Hypertension	0.211	0.296 (0.044-1.996)
Hyperlipemia	0.87	0.852 (0.125-5.827)
SAH	0.527	2.438 (0.154-38.557)
The type of PICA	0.306	2.633 (0.412-16.807)
VADA with saccular structure	0.76	1.345 (0.201-8.98)
VADA in dominant side	0.041	10.492 (1.097-100.39)
The length of the dissection in artery	0.015	1.304 (1.053-1.615)
Intervention therapy
SAC-L	Ref	-
SAC-B	0.094	0.146 (0.015-1.389)
PAO	0.999	0

Abbreviations: SAH, subarachnoid hemorrhage; PICA, posteroinferior cerebellar artery; VADA, vertebral artery dissecting aneurysms; SAC-L, engraving laser stent-assisted coil; SAC-B, regular braided stent-assisted coil; PAO, parent artery occlusion.

FIG. 3. Percentage of DSA radiological outcomes in the different therapy groups.

Abbreviation: SAC-L, engraving laser stent-assisted coil; SAC-B, regular braided stent-assisted coil; PAO, parent artery occlusion.

The pathological examination of dissecting aneurysms revealed that the true lumen was connected to a pseudolumen via a rupture in the internal elastic lamina. This finding underscores the importance of dissection repair as a pivotal aspect of the treatment strategy[8]. Consequently, stent-assisted coil embolization has emerged as the predominant approach for managing VADAs[9]. The deployment of a single stent is typically reserved for dissections affecting extensive segments of the extracranial vertebral artery. Nonetheless, the safety of flow diverter (FD) stent implantation in the posterior circulation warrants further investigation[10, 11]. Recent evidence suggests that the efficacy of braided stent-assisted coil embolization in treating posterior circulation aneurysms surpasses that of laser-cut stents[12]. This observation aligns with our findings, possibly attributed to the denser mesh of braided stents, which enhances their flow-diverting capability compared to laser-cut stents.

The interplay between the posterior inferior cerebellar artery (PICA) and VADA significantly influences surgical planning[13]. However, our study did not identify a direct correlation between this relationship and the outcomes of VADA, diverging from prior research where PICA involvement was deemed a solitary risk factor for recurrence post-endovascular treatment of vertebrobasilar dissecting aneurysms[14]. Such discrepancies may stem from variations in treatment methodologies. Therefore, it can be considered that choosing the right surgical approach may be related to reducing the risk of postoperative recurrence of VADA closely associated with PICA.

It is universally acknowledged that the aneurysm neck width is a crucial parameter for devising surgical strategies and prognosticating outcomes[15]. Yet, accurately measuring the neck width of VADAs poses challenges. Therefore, we opted to measure the length of the arterial dissection as a proxy for neck width. As anticipated, a statistically significant association was found between the dissection length and the recurrence of VADA. For VADA, the arterial wall at the site of dissection usually involves damage to the elastic and fibrous layers, leading to an increased risk area of the dissection continuing to grow into an arterial aneurysm[16]. Thus, the longer the length of the arterial dissection, the greater the risk of recurrence.

Our analysis also indicated that VADAs located on the dominant side were prone to recurrence, potentially due to the higher blood flow in the dominant vertebral artery. This increased flow may exert greater stress on the affected side, compressing the coil[17]. Additionally, surgeons might exercise greater caution when operating on the dominant side to avoid compromising blood flow.

Lastly, we explored the relationship between the presence of a saccular structure in VADAs and the likelihood of postoperative recurrence. A saccular structure, indicative of localized arterial wall thinning, elevates the risk of rupture[18]. Our findings did not reveal a significant link between saccular structures and VADA recurrence. Just like aneurysms in other parts of the brain, larger size also means a need for denser packing, which in turn requires higher skill in filling for surgeons. though the possibility of an underpowered sample size suggests the need for further investigation.

However, this study has several limitations, including its retrospective design, patient selection bias, and a limited number of cases. Therefore, our conclusions need further validation in larger-scale, prospective studies.

Future research should focus on improving treatment strategies for VADA to reduce the risk of recurrence. Additionally, exploring new treatment modalities, such as improved stent designs or novel flow-diverting devices, may help enhance treatment efficacy and reduce the risk of recurrence.

In summary, this study highlights the importance of considering the aneurysm's location on the dominant side, the length of the dissection, and the choice of treatment method when treating VADA. Despite some limitations, our findings provide valuable insights for future research and clinical practice.

This study conducted a retrospective analysis of 63 patients with Vertebral Artery Dissecting Aneurysms (VADA) who underwent interventional therapy from 2015 to 2024, aiming to identify risk factors for VADA recurrence. Our analysis revealed three independent risk factors for recurrence: VADA located on the dominant side, longer length of arterial dissection, and the use of laser-engraved stent-assisted coil (SAC-L) as the interventional treatment method. In contrast, patients treated with regular braided stent-assisted coil (SAC-B) and parent artery occlusion (PAO) demonstrated higher rates of complete occlusion.

These findings have significant implications for improving treatment strategies for VADA. Specifically, they underscore the importance of considering the anatomical location of VADA and the length of arterial dissection when selecting interventional treatment options. Moreover, our study supports the strategy of prioritizing the use of regular braided stent-assisted coil (SAC-B) and parent artery occlusion (PAO) over laser-engraved stent-assisted coil (SAC-L) in the treatment of VADA.

In conclusion, this study provides new insights into the risk factors for VADA recurrence and offers valuable guidance for clinicians on how to choose the best interventional treatment strategies to reduce the risk of recurrence. Despite being subject to limitations such as its retrospective design, patient selection bias, and a limited number of cases, the findings still make a significant contribution to both the academic and practical fields, laying a foundation for future research and clinical practice.

CI Confidence Interval

CT Computed Tomography

CTA Computed Tomography Angiography

DSA Digital Subtraction Angiography

FD Flow Diverter

OR Odds Ratio

PAO Parent artery Occlusion

PED Pipeline Embolization Device

PICA Posteroinferior Cerebellar Artery

SAC-B Regular Braided Stent-assisted Coil

SAC-L Engraving Laser Stent-assisted Coil

SAH Subarachnoid Hemorrhage

VADA Vertebral Artery Dissecting Aneurysms

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

The datasets that were used and evaluated in this study can be obtained from the corresponding author upon making a reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

None.

Author contributions

JY contributed to the conception and design of the study, had full access to all the data in the study. KC and YH contributed to the acquisition of data. KC contributed to the analysis and interpretation of the data. All authors participated in manuscript writing, revision, and approved the submitted version.

Acknowledgements

None.

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No competing interests reported.

Identifying Recurrence Risk Factors in Vertebral Artery Dissecting Aneurysms Post-Intervention

Status:

Version 1

Abstract

Background

Method

Result

Conclusion

Figures

INTRODUCTION

METHOD

RESULTS

DISCUSSION

CONCLUSION

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1