Carotid artery stenting in clinical practice depending on patient age.

BACKGROUND: The age-dependent outcome of carotid artery stenting (CAS) outside of randomized controlled trials is largely unknown. Therefore, we assessed acute and long-term results of CAS in a single-center real-world registry. METHODS: All symptomatic and asymptomatic patients who consecutively underwent CAS were enrolled into the present analysis. The population was divided into three groups dependent on patients' age (<65, 65-74, and ≥75 years). RESULTS: Between 1999 and 2015, a total of 878 patients (24%, <65 years; 40%, 65-74 years; and 36%, ≥75 years) underwent CAS. The rate of the primary endpoint (30-day composite of death, stroke, and myocardial infarction [MACCE] plus long-term ipsilateral stroke) was higher in patients aged ≥75 years compared to the middle-age group (hazard ratio [HR] 2.30, confidence interval [CI] 1.22-4.36; P = 0.001). Similarly, the rate of the stroke endpoint (30-day any stroke plus long-term ipsilateral stroke) was higher in patients aged ≥75 years compared to patients aged 65-74 years (HR 2.03, CI 1.01-4.10; P = 0.04). There was no significant age-dependent difference of the primary endpoint and stroke endpoint in the subset of asymptomatic patients. Furthermore, age had no influence on the risk of stroke beyond the periprocedural period. CONCLUSIONS: Patients aged ≥75 years had poorer outcomes after CAS compared to younger patients. Importantly, age did not influence the outcome in asymptomatic patients and the risk for stroke beyond the periprocedural period.

Incidence and risk factors of embolized particles in carotid artery stenting and association with clinical outcome.

BACKGROUND: One of the mechanisms for periprocedural neurologic events in carotid artery stenting (CAS) is catheter manipulation within the aorta and supraaortic arteries causing plaque embolization. Therefore, the present analysis sought to determine risk factors for embolic particle dimensions and their relationship with adverse clinical events after CAS. METHODS: Between 1999 and 2015 embolic protection devices (EPD) of a total of 944 CAS procedures were evaluated regarding the occurrence and size of captured particles. RESULTS: Particles were found in 819 of 944 (87%) EPDs. Larger particles were detected in procedures using open cell stents (150±282µm vs. 107±177µm; p=0.005) and longer stents (≥40mm) (165±315µm vs. 122±215µm; p=0.026). With increasing learning curve, particle size was continually reduced (168±282µm in the first third of the cohort vs. 127±309µm in the second third vs. 108±114µm in the last third; p=0.009). Longer stents and use of Acculink stent were found to be independent predictors for particle diameter. In patients who died or sustained a stroke during long-term follow-up (median 5.5years [IQR 2.6-7.9]) significantly larger particles were captured during CAS compared to those patients with an uneventful follow-up (160±330µm vs. 121±195µm; p=0.047). CONCLUSIONS: In the vast majority of CAS procedures particles could be retrieved from the EPDs used. Procedural characteristics such as stent type and stent length were associated with larger particles.

Stroke rates after carotid artery stenting depend on study-specific definitions.

AIMS: There is no consensus definition for minor and major stroke in trials comparing CAS vs. CEA. In this study the patients of our large single-centre CAS registry suffering a procedure-related stroke were categorised as minor or major stroke according to study-specific definitions. METHODS AND RESULTS: A board-certified neurologist examined nearly all patients (99%) pre- and post-procedurally, and once again in case of a subsequent neurological deficit. To objectify the deficits the NIHS Scale and modified Rankin Scale (mRS) were used. To compare the difference of the rates of minor and major strokes according to each definition, Fleiss' Kappa and Cohen's Kappa Test were used, as appropriate. Up to 30 days, 34 (3.6%) neurological events in 947 procedures lasting >24 hours (=stroke) occurred. According to our definition (major stroke: symptoms lasting >30 days, NIHSS ≥4 and/or mRS ≥3), 15 (1.6%) sustained a major and 19 (2%) a minor stroke. The comparison of all definitions of stroke resulted in a substantial agreement (Fleiss' Kappa=0.73). The stroke rates depending on available definitions were as follows: our centre 19 minor/15 major strokes, CREST 15/18 (1 n.a.), Yadav et al 14/20, Bamford et al 18/13 (3 n.a.), Post et al 18/13 (3 n.a.), SPACE 17/17, ICSS 22/11 (1 n.a.). CONCLUSIONS: Study-specific definitions for minor and major strokes lead to significantly different rates of stroke. Therefore, study-specific definitions should be respected comparing the results of each trial. A standard definition for minor and major stroke should be used in future trials.

Long-Term Outcomes of Carotid Artery Stenting in Clinical Practice.

BACKGROUND: There is a lack of long-term data and data outside of controlled clinical trials in carotid artery stenting. Thus, we sought to evaluate the long-term effectiveness in stroke prevention by carotid artery stenting in a large number of patients in a real-world setting. METHODS AND RESULTS: The present work represents an all-comer registry with a strict, prospectively designed, follow-up protocol, including an independent pre- and postprocedural neurological assessment. Between November 1999 and March 2015, 1000 procedures in 901 patients were consecutively performed in a single center. Mean age was 71±9 years, and symptomatic stenosis was present in 262 patients (29.1%). The population was also characterized by a high comorbidity: 289 patients (32.1%) would have been excluded according to the CREST protocol (Carotid Revascularization Endarterectomy Versus Stent Trial). The median length of follow-up was 5.5 (interquartile range, 2.6-7.9) years and complete in 93% of the patients. The rate of the primary end point (composite of stroke, death, and myocardial infarction [major adverse cardiac or cerebrovascular event] by day 30 plus ipsilateral stroke beyond 30 days) was 6.9% (9.9% in symptomatic versus 5.7% in asymptomatic patients; P=0.03). The rate was higher in CREST ineligible than in CREST eligible patients (11.4% versus 4.9%; P=0.001). CONCLUSIONS: Long-term stroke prevention by carotid artery stenting is effective in experienced centers. A high percentage of patients who would have been excluded from controlled clinical trials undergoes carotid artery stenting in daily clinical practice. However, these patients have a substantially higher risk for an acute major adverse cardiac or cerebrovascular event.

Oral interferon-alpha treatment of mice with cryoglobulinemic glomerulonephritis.

Cryoglobulins are associated with the development of a membranoproliferative glomerulonephritis, often referred to as cryoglobulinemic glomerulonephritis, particularly in the setting of hepatitis C virus infection. Parenteral interferon-alpha (IFN-alpha) commonly is used therapeutically in humans with cryoglobulinemic glomerulonephritis. We tested the therapeutic impact of oral IFN-alpha treatment in thymic stromal lymphopoietin (TSLP) transgenic mice, a strain that develops mixed cryoglobulinemia with glomerulonephritis closely resembling the disease that occurs in humans. A total of 41 female mice were treated for 21 days with daily ingestion of either 500 IU of Universal type I IFN or placebo. The studied groups included TSLP transgenic mice treated with IFN-alpha (n = 13), TSLP transgenic mice treated with placebo (n = 13), wild-type mice treated with IFN-alpha (n = 5), and wild-type mice treated with placebo (n = 10). A total of 39 mice completed the study; two TSLP transgenic mice treated with IFN-alpha died during the study period. Placebo-treated TSLP transgenic mice showed significantly increased mean glomerular tuft areas, mean glomerular areas occupied by macrophages, and mean cell numbers per glomerulus compared with wild-type controls. All three parameters were decreased in IFN-alpha-treated TSLP transgenic mice, although the differences compared with placebo-treated mice did not reach significance. The changes in glomerular matrix deposition were the same in IFN-alpha-treated and placebo-treated mice. The oral ingestion of IFN-alpha seemed to reduce glomerular macrophage influx, but this did not result in decreased glomerular matrix deposition. The limited positive effect provides experimental support for clinical studies that indicate the beneficial effects of IFN-alpha therapy observed in humans with glomerulonephritis might be attributable to its antiviral effect rather than modulation of intrarenal pathophysiologic pathways.

Predictors of minor versus major stroke during carotid artery stenting: results from the carotid artery stenting (CAS) registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK).

BACKGROUND: Patient outcome, quality of life as well as health care costs differ between patients with minor versus major stroke during carotid artery stenting. Evaluation of predictors for both subtypes of strokes is of paramount importance. METHODS AND RESULTS: We analyzed data from the prospective, web-based German carotid artery stenting (CAS) registry. All patients entered in this registry were included as of January 2011. During the periprocedural period (until patient discharge or transfer) 1.5 % of the patients (85/5,794) sustained a major and 1.3 % (75/5,784) a minor stroke (total periprocedural stroke rate 2.8 %). Mean age of all patients was 71 years, 72 % were male and 50 % had a symptomatic carotid stenosis. Regression analysis identified age (OR 1.44; 95 % CI 1.05-1.98), symptomatic stenosis (OR 3.17; 95 % CI 1.74-5.76) and procedural duration per 10 min (OR 1.22; 95 % CI 1.13-1.31) as independent predictors for major strokes. Age (OR 1.43; 95 % CI 1.03-1.98), diabetes (OR 1.75; 95 % CI 1.04-2.94), and procedural duration (OR 1.17; 95 % CI 1.08-1.27) predicted for minor strokes. The use of an embolic protection device significantly prevented both type of strokes (OR 0.31; 95 % CI 0.15-0.62 for major strokes; OR 0.40; 95 % CI 0.18-0.91 for minor strokes), female patients suffered less major strokes (OR 0.47; 95 % CI 0.24-0.92). Moreover, minor and major strokes were associated with death, contralateral embolism and a longer hospital stay more frequently. CONCLUSION: Patients with one or more risk factors for periprocedural stroke seem to require special attention in terms of optimal preprocedural assessment of the carotid stenosis and vascular anatomy, as well as adequate patient preparation. Identifying these risk factors may help in patient selection, encourage further refinement in carotid artery stenting technique and avoid procedural complications. The use of an embolic protection device system was associated with less periprocedural minor and major strokes.

The role of endovascular expertise in carotid artery stenting: results from the ALKK-CAS-Registry in 5,535 patients.

PURPOSE: Several scientific committees have proposed an accentuation of operator minimal requirements before accreditation for carotid artery stenting is granted. The current study aims to identify potential effects from increasing site experience on periprocedural safety and outcome of carotid artery stenting (CAS). METHODS: Between 1996 and December 2009, 5,535 procedures have been entered into the prospective, controlled ALKK-CAS-Registry. The total cohort was divided in four subgroups according to the consecutive patient order at each participating center: patients 1-49 (n = 1,485), 50-99 (n = 1,118), 100-199 (n = 1,521) and ≥200 (n = 1,411). RESULTS: The median age of all patients was 71 years; 52.8 % had a symptomatic carotid stenosis. A decline in the rates of in-hospital major stroke (2.1, 1.9, 1.6, 0.9, p for trend 0.014) and of ipsilateral strokes (3.1, 2.4, 2.5, 1.6 %, p for trend 0.019) was substantiated with increasing site experience. This significant trend was preserved in the combined rate of major stroke and death (4.0, 3.2, 3.4, 2.4 %, p for trend 0.034). Apart from CAS experience, improvements in CAS technique, a decreasing number of symptomatic patients and an increasing number of procedures under embolic protection (each p for trend <0.05) might have contributed to these results. CONCLUSIONS: The results show a gradual reduction of in-hospital stroke rates with increasing center experience. Extensive supervision of CAS learners and further promotion of proctorship programs seem to be essential.