Article Text

Original research
Association of residual stenosis after balloon angioplasty with vessel wall geometries in intracranial atherosclerosis
  1. Zhikai Hou1,2,
  2. Zhe Zhang2,3,
  3. Long Yan1,2,
  4. Jidong You1,2,
  5. Min Wan1,2,
  6. Jia Song1,2,
  7. Yuesong Pan2,
  8. Ferdinand Hui4,
  9. Zhongrong Miao1,2,
  10. Xin Lou5,
  11. Yongjun Wang2,6,
  12. Jing Jing2,3,6,
  13. Ning Ma1,2
  1. 1 Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  2. 2 China National Clinical Research Center for Neurological Diseases, Beijing, China
  3. 3 Tiantan Neuroimaging Center of Excellence, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  4. 4 Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, Maryland, USA
  5. 5 Department of Radiology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
  6. 6 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  1. Correspondence to Dr Ning Ma, Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Beijing, China; maning_03{at}hotmail.com; Dr Jing Jing, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; jingj_bjttyy{at}163.com

Abstract

Background Percutaneous transluminal balloon angioplasty (PTBA) may be an alternative treatment for patients with symptomatic intracranial atherosclerotic disease (ICAD) refractory to medical treatment. This study aimed to investigate the association of vessel wall geometric characteristics on high-resolution magnetic resonance vessel wall imaging (MR-VWI) with low residual stenosis in patients with ICAD after PTBA.

Methods Patients with symptomatic ICAD who underwent PTBA were prospectively and consecutively enrolled. High-resolution MR-VWI was performed before the PTBA. Vessel wall geometries of the target artery, including normalized wall index (NWI: wall area/vessel area × 100%), normalized wall thickness index (NWTI: mean wall thickness/vessel radius × 100%), and remodeling index (RI) were evaluated. Low residual stenosis was defined as postprocedural stenosis degree ≤50%. Perioperative complications including symptomatic ischemic stroke/intracranial hemorrhage, death, and arterial dissection were recorded. The baseline characteristics, vessel wall geometries, and perioperative complications were compared between the patients with low residual stenosis and high residual stenosis.

Results Among 60 patients prospectively enrolled, low residual stenosis was achieved in 46 participants (77%). Three patients (5%) suffered from symptomatic ischemic stroke within 30 days. Multivariable logistic regression showed that a lower NWI and lower NWTI were associated with low residual stenosis after PTBA (adjusted OR 0.57, 95% CI 0.35 to 0.94, p=0.027; and adjusted OR 0.88, 95% CI 0.80 to 0.98, p=0.015).

Conclusions Lower NWI and NWTI of the target artery on high-resolution MR-VWI were associated with low residual stenosis in patients with ICAD after PTBA.

  • angioplasty
  • vessel wall
  • stroke
  • plaque

Data availability statement

Data are available upon reasonable request.

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Introduction

Intracranial atherosclerotic disease (ICAD) is one of the major causes of ischemic stroke worldwide.1–3 The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial showed a higher 30-day rate of cerebrovascular events or death in the stenting group than the medical group (14.7% vs 5.8%) and no benefit of stenting beyond the periprocedural period.4 However, the hemodynamic insufficiency subgroup in the SAMMPRIS medical arm had the highest risk of recurrent stroke (37%).5 There is a subset of patients who have recurrence or progression of symptoms despite the best medical management in the real world.6 Endovascular revascularization treatment with blood flow augmentation may decrease stroke recurrence in these patients.7 8

Recent studies showed percutaneous transluminal balloon angioplasty (PTBA) might be a promising alternative to aggressive medical treatment for patients with ICAD.7 8 A meta-analysis showed that the 30-day and 1-year rate of stroke or death were, respectively, 5% and 9% in ICAD patients treated with PTBA.7 However, the immediate residual stenosis of PTBA caused by the vessel wall recoil is usually higher than intracranial stenting (45.0% vs 28.3% reported in the Wingspan Stent System Post Market Surveillance (WEAVE) trial).9 10 The efficacy of PTBA may be associated with the vessel wall geometric characteristics. High-resolution magnetic resonance vessel wall imaging (MR-VWI) can visualize the vessel wall and assess the characteristics of vessel wall pathology.11–14

In this study, we aimed to investigate which vessel wall geometric characteristics on high-resolution MR-VWI were associated with low residual stenosis in patients with ICAD after PTBA.

Methods

Study design and participants

The data that support the findings of this study are available from the corresponding author on reasonable request. This was a prospective, single-arm, exploratory study of consecutive patients with symptomatic ICAD from an endovascular treatment team in a national stroke center. The study protocol was approved by the institutional review board of Beijing Tiantan Hospital. Written informed consent was obtained from the patients or their legal guardians. Inclusion criteria were: (1) age ≥18 years; (2) ischemic stroke or transient ischemic attack attributed to ≥70% stenosis of a major intracranial artery (including the middle cerebral artery, intracranial carotid artery, basilar artery, and intracranial vertebral artery), which was confirmed by digital subtraction angioplasty—in cases with tandem intracranial stenoses, the most severe stenosis was considered as the responsible lesion; (3) patients refractory to aggressive medical treatment, including dual antiplatelet therapy and intensive management of risk factors; (4) preprocedural modified Rankin Scale (mRS) ≤2; (5) two or more atherosclerotic risk factors including hypertension, hyperlipidemia, diabetes mellitus, and cigarette smoking. Patients with non-atherosclerotic stenosis, concomitant with extracranial stenosis >50% and with intracranial aneurysms in the target artery, were excluded.

MR-VWI protocols and evaluation of vessel wall geometries

All subjects underwent high-resolution MR-VWI within 3 days before PTBA. High-resolution T1-weighted MR-VWI was performed on a 3T MR scanner (MAGNETOM Prisma; Siemens Healthineers, Erlangen, Germany) using a 64-channel head/neck coil. MR-VWI was performed using 3D T1-weighted turbo spin-echo sequences with the following parameters: repetition time/echo time 760 ms/15 ms, slice partial Fourier factor 0.75, turbo factor 60, echo spacing 4.52 ms, and parallel imaging acceleration 3. The field of view was 240 mm×220 mm×172 mm (Foot-Head × Anterior-Posterior × Right-Left) and voxel size was 0.54 mm×0.54 mm×0.54 mm. The scan time for T1-weighted MR-VWI was 6 min 57 s. Other MRI scans included diffusion-weighted imaging, non-contrast MR angiography, susceptibility-weighted imaging, and T2-weighted imaging.

All MR-VWI images of responsible lesions were reconstructed and processed into cross-sectional areas (perpendicular to the vessel) with 0.5 mm slice thickness using commercially available software (VesselMass; Leiden University Medical Center, Leiden, The Netherlands). The evaluation was performed on the reformatted images. The lumen area, vessel area and mean wall thickness were calculated after the manual lumen and vessel contour tracing in the software. The vessel wall area was defined as the difference between the vessel and lumen areas (ie, wall area=vessel area−lumen area). The normalized wall index (NWI) was regarded as the ratio of the vessel wall area to the vessel area at the maximal stenosis site.15 16 The normalized wall thickness index (NWTI) was defined as the ratio of the mean wall thickness to the vessel radius at the maximal stenosis site. The remodeling index (RI) was the ratio of the vessel area at the maximal stenosis site to that of the reference site (figure 1).17 18 The reference site was chosen using the WASID (Comparison of Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis) method.19

Figure 1

Schematic diagram of vessel wall geometries. The diagram shows the measurement of normalized wall index, normalized wall thickness index, and remodeling index. ACA, anterior cerebral artery; ICA, internal carotid artery; MCA, middle cerebral artery.

All vessel wall images were interpreted by two neurologists (ZKH with more than 3 years’ experience and JJ with more than 5 years’ experience) with consensus. A third reader (XL with more than 10 years’ experience) was invited to resolve any disagreements which arose.

PTBA protocols

All subjects underwent PTBA after at least 5 days of a dual antiplatelet regimen of aspirin (100 mg/day) and clopidogrel (75 mg/day). All procedures were performed under general anesthesia and by a qualified neurointerventionalist. After vascular access was achieved, intravenous heparin was administered via a bolus (75 U/kg) followed by half the dose 1 hour later; if the procedure lasted longer than 2 hours, a quarter of the initial dose was given every hour thereafter. The guide catheter was advanced into the cervical vertebral or internal carotid artery as high as vessel tortuosity allowed. A 0.014 inch guidewire was carefully manipulated across the lesion, and then a balloon catheter was advanced through the stenosis over a microwire. When the target artery was too tortuous or there was very severe stenosis or an occlusive lesion, a microwire was advanced coaxially through a microcatheter. After the microwire crossed the lesion and reached a safe zone, the microcatheter would be exchanged for the balloon catheter. Underdilation was performed to avoid arterial dissection, vessel rupture, and the snowplow effect of compressed plaque into perforator arteries. The balloon size was 80% of actual normal vessel luminal diameter or 60% in lesions directly adjacent to angiographically visible perforators.10 The balloon length covered the lesion totally.

Non-contrast CT was performed. The periprocedural medical treatment was the same as a previous study.10 If the blood pressure was over 140/90 mm Hg, oral or intravenous antihypertensive treatment was required for lowering the risk of hyperperfusion injury.

Low residual stenosis was defined as postprocedural stenosis degree ≤50% on digital subtraction angiography based on the WASID method.20 If the antegrade blood flow after PTBA was normal (modified Thrombolysis In Cerebral Infarction 3), rescue stenting was not performed.21 Perioperative complications included symptomatic ischemic stroke, symptomatic intracranial hemorrhage, death, and arterial dissection. Symptomatic ischemic stroke is defined as a new focal neurologic deficit of sudden onset due to ischemic stroke, lasting at least 24 hours. Symptomatic intracranial hemorrhage is defined as a parenchymal, subarachnoid, or intraventricular hemorrhage that is associated with a seizure or with a new neurologic deficit, lasting at least 24 hours.

Dual antiplatelet therapy was maintained for at least 3 months after the procedure. Risk factor control was performed to achieve the following: systolic blood pressure <140 mm Hg (or 130 mm Hg in patients with diabetes mellitus), low-density lipoprotein <70 mg/dL, or a decrease by 50%, smoking cessation, and lifestyle modifications.4

Statistical analysis

Continuous variables are presented as mean±SD or median with IQR; categorical variables are presented as percentages. The differences in sex, vascular risk factors, qualifying events, and qualifying arteries between the low residual stenosis group and the high residual stenosis group were assessed by χ2 test or Fisher’s exact test. The differences in age, time from the initial qualifying event to VWI, preprocedural stenosis, lesion length, and vessel wall geometries on high-resolution MR-VWI between the low residual stenosis group and the high residual stenosis group were compared using the Student’s t-test or Mann-Whitney test. The differences of vessel wall geometries on high-resolution MR-VWI between these two groups were assessed using the univariable logistic regression and further using the multivariable logistic regression. We adjusted the age and sex in the multivariable logistic regression. Adjusted odds ratio (OR) and 95% confidence interval (95% CI) were calculated. A two-sided p value <0.05 indicated statistical significance. All statistical analyses were performed using commercial SPSS 21.0 software.

Results

Patient baseline characteristics

The flow chart of this study is shown in online supplemental figure 1. From April 2020 to February 2021, 148 patients with intracranial atherosclerosis were admitted to our center. Patients with stenosis <70% (n=20) and patients who refused to participate in the study (n=66) were excluded. Of the 62 patients assessed for eligibility, two patients were excluded because of concomitant aneurysms in the target artery. Sixty patients with ICAD were enrolled and underwent PTBA. The baseline characteristics of the patients are summarized in online supplemental table 1. The mean age was 58.4±11.87 years. There were 44 (73.3%) men and 16 (26.7%) women. All patients had an mRS ≤1 at enrollment. Thirty-five (58.3%) had ischemic stroke, and 25 (41.7%) had transient ischemic attack as their presenting symptoms. Fifty-six patients underwent PTBA with Gateway balloon (Stryker, Natick, MA), two patients with Emerge Monorail balloon (Boston Scientific, Marlborough, MN), and two patients with Neuro RX balloon (Sino Medical Sciences, TEDA, Tianjin, China).

The mean preprocedural and postprocedural stenosis was 88.34±10.47% and 38.86±16.11%. The qualifying arteries were middle cerebral artery in 22 patients (36.7%), internal carotid artery in five (8.3%), basilar artery in 23 (38.3%), and intracranial vertebral artery in 10 (16.7%). The median time from the initial qualifying event to MR-VWI was 60 (IQR 30–90) days. Three patients (5%) suffered from symptomatic ischemic stroke within 30 days. However, none of them was disabling. There was no symptomatic intracranial hemorrhage, death, or arterial dissections.

Comparison of baseline features, vessel wall geometries, and perioperative complications between the low residual stenosis and high residual stenosis groups

One patient with procedural failure occurred because attempts to pass the balloon through the stenotic lesion were unsuccessful. Of the 59 patients with procedural success, postprocedural residual stenosis ≤50% on angiogram was achieved in 46 patients (77%) (figure 2). There were no significant differences in age, sex, vascular risk factors, qualifying events, and qualifying arteries. There were no significant differences in preprocedural stenosis degree and length of lesions between the two groups. Furthermore, there was no significant difference in the rate of symptomatic ischemic stroke between the low residual stenosis group and the high residual stenosis group (table 1).

Figure 2

(A) Digital subtraction angiography showing severe stenosis located at the proximal segment of the basilar artery. (B) The stenosis was confirmed by longitudinal-section reconstructions on magnetic resonance vessel wall imaging. (C) Reconstructed cross-section vessel wall images were used to measure vessel wall geometries. The normalized wall index (NWI) of the basilar artery was 96.00%, the normalized wall thickness index (NWTI) was 80.24%, and the remodeling index (RI) was 0.70. (D) The lesion was dilated with a 2.25×15 mm Gateway balloon (Stryker, Natick, MA). After the procedure, the stenosis improved from 85% to 23%. (E) Digital subtraction angiography showing right middle cerebral artery total occlusion. (F) The stenosis was confirmed by longitudinal-section reconstructions on magnetic resonance vessel wall imaging. (G) The NWI of the middle cerebral artery was 100.00%, the NWTI was 100.00%, and the RI was 0.44. (H) The lesion was dilated with a 1.5×15 mm Gateway balloon. After the procedure, the residual stenosis was 63%.

Table 1

Comparison of baseline features, vessel wall geometries, and perioperative complications between the low residual stenosis group and the high residual stenosis group

In terms of vessel wall geometries on VWI, the low residual stenosis group had a lower NWI and lower NWTI than the high residual stenosis group (97.00% vs 99.00%, OR 0.59, 95% CI 0.36 to 0.95, p=0.029; and 85.87% vs 93.42%, OR 0.90, 95% CI 0.82 to 0.98, p=0.019). Multivariable logistic regression showed that a lower NWI and lower NWTI were also associated with a lower degree of residual stenosis (≤50%) after PTBA (adjusted OR 0.57, 95% CI 0.35 to 0.94, p=0.027; and adjusted OR 0.88, 95% CI 0.80 to 0.98, p=0.015). There are no significant differences in RI between the two groups (table 2).

Table 2

Comparison of vessel wall geometries between the low residual stenosis group and the high residual stenosis group

Discussion

In this study, we prospectively acquired a high-resolution MR-VWI database consisting of a group of symptomatic ICAD patients treated with PTBA, and systematically investigated the immediate efficacy of PTBA in patients with symptomatic ICAD using the modality of advanced three-dimensional MR-VWI. The major finding of our study was that in patients with symptomatic ICAD treated with balloon angioplasty, a better immediate outcome (postprocedural residual stenosis ≤50%) after balloon angioplasty may be associated with a lower NWI and NWTI on high-resolution MR-VWI. Furthermore, the 30-day incidence of symptomatic ischemic stroke and death (5%) was comparable with the previous studies (5–9%).7

The finding that the short-term efficacy of PTBA for intracranial atherosclerosis was associated with vessel wall geometries on high-resolution MR-VWI has not previously been well established in the literature. In this study, we used the normalized metrics (NWI, NWTI, and RI) of the vessel wall to standardize the plaque burden and vessel wall thickness evaluation, enabling the comparison of plaques in vessel segments of varying sizes.15 The index NWI/NWTI may be more objective than RI (NWI and NWTI do not require the selection of a reference site, as does RI) and may reflect the vessel wall pathology instead of the lumen. A higher NWI indicated that the vessel wall area at the maximal stenosis site was relatively larger, and a higher NWTI meant the wall thickness of the lesion was relatively thicker. The atherosclerotic vessel wall will develop resistance to the balloon in the process of mechanical expansion. The higher the NWI and NWTI of the intracranial artery, the stronger is the resistance to mechanical dilation of the balloon. There is a more obvious wall recoil in these patients with higher NWI and NWTI. This finding may suggest that patients with a higher NWI or NWTI should undergo stenting instead of PTBA alone due to the high likelihood of wall recoil.

The SAMMPRIS study showed that the 1 year rate of stroke or death in the stenting group was higher than in the medical group (20.0% vs 12.2%), and most of them occurred in the perioperative period.4 22 It reminded us that endovascular treatments may still be helpful in symptomatic ICAD if the perioperative complication was minimized. In our study, the 30-day incidence of symptomatic ischemic stroke and death was 5%. Furthermore, there was no iatrogenic vessel dissection after the procedure. The result was comparable with the medical group in the SAMMPRIS study and previous balloon angioplasty studies.7 23 24 The finding suggested that PTBA with submaximal balloon dilation may be relatively safe for ICAD. The rate of postprocedural stenosis ≤50% was 77% in this study. A recent meta-analysis demonstrated that the overall technical success rate of PTBA was 93% (95% CI 85% to 98%).7 The differences in technical success rate can be explained by the study design, diverse definition of technical success, and various enrolled participants.

The study has some limitations. First, we just investigated the vessel wall geometries associated with only the immediate residual stenosis of PTBA in our study. The long-term outcome of PTBA remains uncertain, and we are conducting follow-ups of these patients with ICAD. The long-term restenosis rates need to be evaluated with longitudinal studies. Second, six patients with intracranial occlusion were enrolled in this study. Without gadolinium-based MR contrast agents, the detailed plaque characteristics may be difficult to evaluate in these patients with complete intracranial occlusion. Thirdly, this was a single-center study involving a small number of patients of Chinese ethnicity only, which may cause a type II error. Therefore, the study findings need to be confirmed in a larger cohort study including a multi-ethnic population.

Conclusions

In summary, the immediate dilation efficacy of PTBA may be associated with the vessel wall geometries on high-resolution MR-VWI. A better immediate dilation efficacy (residual stenosis ≤50%) after PTBA was associated with a lower preprocedural NWI and NWTI on high-resolution MR-VWI. These findings need to be confirmed or refuted in future studies.

Data availability statement

Data are available upon reasonable request.

Ethics statements

Patient consent for publication

Ethics approval

The Ethics Committee of Beijing Tiantan Hospital approved this study under identification number KY2019-083-03. Written informed consent was obtained from the patients or their legal guardians before taking part.

Acknowledgments

We thank Liqian Sun, Yuhua Jiang, Ming Yang, Guangyin Zuo, Huaming Wei, Dongxu Yang, Jinli Gao, Qiqiu Lu, Peng Sun for their assistance with the trial operation.

References

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • ZH and ZZ contributed equally.

  • Contributors ZKH, ZZ, JJ, NM: study concept and design, data analysis, drafting the manuscript, and full responsibility of data. LY, JDY, MW, JS: data collection. ZKH, JJ, XL: imaging data analysis. YSP: data analysis. FH: revising the manuscript. ZRM, XL, YJW: study concept and design of the work. All authors approved the final version to be published. They agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the manuscript are appropriately investigated and resolved.

  • Funding This study was supported by the National Natural Science Foundation of China (Contract grant number: 81471390 to NM, 81825012 and 81730048 to XL). Specialized in clinical medical development - 'Yangfan Plan' (XMLX201844 to NM).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.