Submaximal angioplasty for symptomatic intracranial atherosclerosis: a prospective Phase I study.

OBJECTIVE Intracranial atherosclerotic disease (ICAD) accounts for approximately 10% of ischemic strokes. The recent Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study demonstrated a high incidence of perioperative complications (15%) for treatment of ICAD with stenting. Although the incidence of stroke was lower in the medical arm, recurrent stroke was found in 12% of patients despite aggressive medical management, suggesting that intervention may remain a viable option for ICAD if perioperative risk is minimized. Angioplasty without stenting represents an alternative and understudied revascularization treatment for ICAD. Submaximal angioplasty limits the risks of thromboembolism, vessel perforation, and reperfusion hemorrhage that were frequently reported with stenting in the SAMMPRIS trial. The authors conducted a prospective Phase I trial designed to assess the safety of submaximal angioplasty in patients with symptomatic ICAD. METHODS This study was approved by the local institutional review board. Demographic and clinical data were prospectively collected. Angioplasty was performed with a balloon undersized to approximately 50%-70% of the nondiseased vessel diameter in patients with symptomatic ICAD who had angiographically significant stenosis of ≥ 70%. The primary outcome measure was the incidence of periprocedural complications (combined rate of death, stroke, and hemorrhage occurring within 30 days and at 1 year). RESULTS Among the 65 patients with symptomatic ICAD who were screened, 24 had significant angiographic stenosis that met the inclusion criteria of this study. The mean age was 64.08 years (median 65 years; SD ± 11.24 years), most were men (62.5%), and most were white (66.67%). Many patients had concomitants of vascular disease, including hypertension (95.8%), hyperlipidemia (70.83%), smoking history (54.1%), and diabetes mellitus (50.0%). Coronary artery disease (41.66%) and previous stroke or transient ischemic attack (45.83%) were frequently present. Most patients (75%) had anterior circulation stenosis. The mean preprocedure stenosis was 80.16% (median 80%, range 70%-95%). Submaximal angioplasty was performed in patients who met the inclusion criteria, with a mean postangioplasty stenosis rate of 54.62% (median 55.5%, range 31%-78%). Rates of ischemic stroke in the territory of the treated artery were 0% within 30 days and 5.55% (in the only patient who presented with recurrent stroke) at 1 year. The mortality and hemorrhage rates in this series were 0%. CONCLUSIONS This study demonstrates the safety of the submaximal angioplasty technique, with no permanent periprocedural complications in 24 treated patients.

CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease.

OBJECT Symptomatic intracranial atherosclerotic disease (ICAD) has a high risk of recurrent stroke. Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients, but have not been studied in ICAD. The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms (SNPs) in symptomatic ICAD patients. METHODS Genotype testing for CYP2C19*2, (*)3, (*)8, (*)17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin. Testing was performed prospectively at 1 center, and retrospectively from a DNA sample biorepository at 2 centers. Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint, which was a composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 months. RESULTS The primary endpoint occurred in 14.9% of the 188 cases. In multiple logistic regression analysis, the presence of the CYP2C19 loss of function (LOF) alleles *2, *3, and *8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes (odds ratio [OR] 0.13, 95% CI 0.03-0.62, p = 0.0101). Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint, with hazard ratio (HR) of 0.27 (95% CI 0.08-0.95), p = 0.041. A sensitivity analysis of a secondary composite endpoint of TIA, stroke, or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants, with lower odds of secondary endpoint in patients carrying at least 1 LOF allele (*2, *3, *8) than in wild-type homozygotes (OR 0.27, 95% CI 0.06-1.16, p = 0.078). Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint (HR 0.22, 95% CI 0.05-1.04, p = 0.056). CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD. Variant alleles of CYP2C19 (*2, *3, *8) were associated with lower odds of the primary and secondary composite endpoints. However, the direction of the association was opposite of what is expected based on this SNP. This may reflect an incomplete understanding of this genetic variation and its effect in symptomatic ICAD and warrants further investigations.

Superior performance of cone-beam CT angiography in characterization of intracranial atherosclerosis.

OBJECT: Intracranial atherosclerotic disease (ICAD) carries a high risk of stroke. Evaluation of ICAD has focused on assessing the absolute degree of stenosis, although plaque morphology has recently demonstrated increasing relevance. The authors provide the first report of the use of ultra-high-resolution C-arm cone-beam CT angiography (CBCT-A) in the evaluation of vessel stenosis as well as plaque morphology. METHODS: Between August 2009 and July 2012, CBCT-A was used in all patients with ICAD who underwent catheter-based angiography at the authors' institution (n = 18). Lesions were evaluated for maximum degree of stenosis as well as plaque morphological characteristics (ulcerated, calcified, dissected, or spiculated) via digital subtraction angiography (DSA), 3D-rotational angiography (3DRA), and CBCT-A. The different imaging modalities were compared in their assessment of absolute stenosis as well as their ability to resolve different plaque morphologies. RESULTS: Lesions were found to have similar degrees of stenosis when utilizing CBCT-A compared with 3DRA, but both 3DRA and CBCT-A differed from DSA in their assessment of the absolute degree of stenosis. CBCT-A provided the most detailed resolution of plaque morphology, identifying a new plaque characteristic in 61% of patients (n = 11) when compared with DSA and 50% (n = 9) when compared with 3DRA. CBCT-A identified all lesion characteristics visualized on DSA and 3DRA. CONCLUSIONS: CBCT-A provides detailed spatial resolution of plaque morphology and may add to DSA and 3DRA in the evaluation of ICAD. Further prospective study is warranted to determine any benefit CBCTA-A may provide in clinical decision making and risk stratification over existing conventional imaging modalities.