Patient Selection
We retrospectively studied consecutive patients who underwent selective primary balloon angioplasty and stenting for symptomatic atherosclerotic intracranial artery stenosis from the prospectively acquired endovascular treatment databases of our institution between April 2006 and September 2020. Informed consent for the procedure was obtained from all patients. The study protocol was approved by the ethics review board of our institution.
Our inclusion criteria were: (1) patients with ≥ 70% stenosis of the main trunk of the middle cerebral artery (MCA), internal carotid artery (ICA), vertebral artery (VA), or basilar artery (BA) on cerebral angiography; (2) those with a history of a stenotic-lesion-induced transient ischemic attack (TIA) or non-disabling ischemic stroke (mRS ≤ 2); and (3) interval from the last TIA or ischemic stroke ≥ 72 hours. Our exclusion criteria were: (1) residual stenosis immediately after recanalization therapy for acute major intracranial artery occlusion, (2) the presence of tandem extracranial lesions, and (3) pretreatment modified Rankin Scale score ≥ 3. We performed diagnostic imaging including cerebral angiography for patients with symptomatic ICAS, and initially start medical treatment. All patients received optimal medical treatment according to the guidelines at the time of treatment. For endovascular treatment, patients were selected in consideration of the indication criteria and exclusion criteria of our institution, and treatment is performed when consent is obtained from the patients and their families. Endovascular treatment was usually performed more than 2 weeks after the most recent onset.
Diagnostic criteria for atherosclerotic intracranial artery stenosis were as follows: (1) the absence of cerebral artery dissection on cerebral angiography, and (2) patients with ≥ 2 of the following vascular risk factors: hypertension, dyslipidemia, diabetes mellitus (DM), peripheral arterial disease, coronary artery disease, smoking, pre-existing atherosclerotic stenosis in other locations, and the presence of aortic plaque. Patients with ischemic stroke perform carotid echography, electrocardiogram, echocardiography, and transesophageal echocardiography to search for embolic sources in order to evaluate the etiology of ischemic stroke. Various blood tests and cerebrospinal fluid tests are performed to distinguish inflammatory diseases. If arterial dissection is suspected, in addition to cerebral angiography, MRA and CTA are repeated to check for morphological changes. These diagnostic studies were repeated when the stroke recurred.
The following procedures were established as standards for minimally invasive combination therapy at our institution: (1) as initial treatment, primary balloon angioplasty alone was performed, (2) stenting was conducted when balloon angioplasty lead to insufficient dilation or acute dissection, (3) stenting should be prioritized for restenotic lesions, and (4) coronary stents were used until July 2014, when the Wingspan stent was approved. Since then, Wingspan stents have been used. Two experienced neuro-interventionalists were responsible for all treatments.
In all patients, MRI/MRA was performed before treatment to evaluate infarcted cerebral foci. The ICA was classified into supraclinoid (C1-C2), cavernous (C3-C4), and petrous (C5) segments. In this study, perioperative complications within 30 days were evaluated as initial results and restenosis, and recurrent ischemic events during follow-up were evaluated as long-term outcomes. Furthermore, factors associated with restenosis and recurrent ischemic events were analyzed.
Interventional Techniques
All treatments were performed under venous anesthesia with propofol and local anesthesia at the site of femoral artery puncture. After a 6-Fr guiding catheter was inserted into the distal cervical internal carotid artery or distal vertebral artery, 5,000 units of heparin was intravenously administered. Percent stenosis was evaluated using the WASID method [10]. In addition, the lesion length and shape (eccentric or concentric) were assessed.
A 0.014-inch microguidewire was guided into a distal artery vessel across the target lesion, then a Gateway balloon catheter (Stryker, Kalamazoo, MI, USA) or Unryu balloon catheter (Kaneka Medics, Tokyo, Japan) was guided. The catheter measured 1.5 to 4.0 mm in diameter, slightly smaller than that of a normal artery distal to the site of stenosis, and 9 to 20 mm in length in accordance with the length of the stenotic site. The balloon catheter was dilated to a maximum atmospheric pressure of 6 atm by increasing the pressure by 1 atm every 10 seconds, and maintained for approximately 30 seconds. When the percent stenosis after dilatation was ≤ 50%, the procedure was regarded as successful. To evaluate the presence of elastic recoiling or dissection after dilatation, repeat angiography was performed several times. When acute dissection with distal blood flow deterioration or residual stenosis of 50% or more were observed, stenting was conducted. After treatment, neurological assessment was conducted and the patients were managed in the intensive care unit until the day after treatment. Anticoagulant therapy with heparin was discontinued.
Periprocedural Assessment
In all patients, MRI/MRA was performed the day after treatment. As procedure-associated complications within 24 hours after treatment, we evaluated arterial dissection, vascular perforation, distal artery occlusion, acute occlusion, and acute in-stent thrombosis. Furthermore, we evaluated all ischemic events, systemic complications, and deaths within 30 days.
Medical Management
Dual antiplatelet therapy (DAPT) was performed from at least 1 week before treatment. Aspirin and clopidogrel were administered to most patients; however, cilostazol was administered to patients treated by Wingspan stent who had clopidogrel resistance, which was based on platelet aggregation evaluated by the VerifyNow P2Y12 Assay (Accumetrics Inc., San Diego, CA, USA). Single antiplatelet therapy (SAPT) was started the day after treatment in patients who underwent balloon angioplasty alone. When stenting was conducted, DAPT was continued for 6 months and switched to SAPT in the ischemic event- or restenosis-free patients. Risk factor control in the patients consisted of achieving systolic blood pressure less than 140 mmHg, the administration of statins for dyslipidemia, and blood glucose control for DM.
Follow-up Management
MRI and cerebral angiography were performed after 6 months to evaluate the presence of restenosis. Subsequently, MRI and MRA were conducted every 6 to 12 months. In this study, restenosis was defined as ≥ 50% stenosis. Recurrent ischemic events (cerebral infarction or TIA) were assessed in all regions in addition to the treated stenotic artery. Restenosis patients with recurrence of ipsilateral ischemic events were retreated with balloon angioplasty or stenting. Medical treatment was continued for asymptomatic restenosis patients. However, if the degree of restenosis progressed in a relatively short period of time, retreatment was considered. Additional treatment was indicated for the following patients: (1) those with ≥ 70% restenosis within 1 year after treatment, and (2) those with ≥ 50% restenosis with recurrent ischemic events. As long-term outcomes, restenosis and recurrent ischemic events were analyzed.
Statistical Analysis
Continuous variables were expressed as mean ± standard deviation. Continuous variables with non-normal distribution were summarized as medians (interquartile range). Categorical variables were presented as numbers and percentages.
Restenosis-associated factors included age, sex, vascular risk factors (hypertension, dyslipidemia, DM, coronary artery disease, and chronic kidney disease), stenotic artery (MCA, ICA, VA and BA), duration from last attack to treatment, percent stenosis before and after treatment, treatment procedure, length and shape of the stenotic lesion, maximum diameter of the balloon catheter or stent, and recurrence of ischemic events (TIA and ischemic stroke). Logistic univariate analysis was used for the factors that influenced the development of restenosis. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox proportional hazards regression models. A p-value < 0.05 was considered statistically significant. All statistical analyses were performed with SPSS (version 9.4, IBM, USA)