Clinical impact and predictors of carotid artery in-stent restenosis

To assess the incidence and clinical significance as well as predictors of in-stent restenosis (ISR) after carotid artery stenting (CAS) diagnosed with serial duplex sonography investigations. We analyzed 215 CAS procedures that had clinical and serial carotid duplex ultrasound investigations. The incidence of in-stent restenosis (ISR) and periprocedural as well as long-term clinical complications were recorded. The influence of an ISR on clinical complication was analyzed using Kaplan-Meier curves and clinical risk factors for the development of an ISR with multivariate logistic regression. During a median follow-up time of 33.4 months (interquartile range 15.3–53.7) an ISR of ≥70% was detected in 12 (6.1%) of 215 arteries (mean age of 68.1 ± 9.8 years, 71.6% male). The combined stroke and death rate during long-term follow-up was significantly higher in the group with an ISR [odds ratio (OR): 3.59, 95% confidence interval (CI): 1.50–8.59, p = 0.004]. After applying multivariate logistic regression analysis contralateral carotid occlusion (OR 10.11, 95% CI 2.06–49.63, p = 0.004), carotid endarterectomy (CEA) restenosis (OR 8.87, 95% CI 1.68–46.84, p = 0.010) and postprocedural carotid duplex ultrasound with a PSV ≥120 cm/s (OR 6.33, 95% CI 1.27–31.44, p = 0.024) were independent predictors of ISR. ISR after CAS during long-term follow-up is associated with a higher proportion of clinical complications. A close follow-up is suggested especially in those patients with the aforementioned independent predictors of an ISR. Against the background of a lacking established treatment of ISR, these findings should be taken into account when offering CAS as a treatment alternative to CEA

Inflammation and In-Stent Restenosis: The Role of Serum Markers and Stent Characteristics in Carotid Artery Stenting

BACKGROUND: Carotid angioplasty and stenting (CAS) may currently be recommended especially in younger patients with a high-grade carotid artery stenosis. However, evidence is accumulating that in-stent restenosis (ISR) could be an important factor endangering the long-term efficacy of CAS. The aim of this study was to investigate the influence of inflammatory serum markers and procedure-related factors on ISR as diagnosed with duplex sonography. METHODS: We analyzed 210 CAS procedures in 194 patients which were done at a single university hospital between May 2003 and June 2010. Periprocedural C-reactive protein (CRP) and leukocyte count as well as stent design and geometry, and other periprocedural factors were analyzed with respect to the occurrence of an ISR as diagnosed with serial carotid duplex ultrasound investigations during clinical long-term follow-up. RESULTS: Over a median of 33.4 months follow-up (IQR: 14.9-53.7) of 210 procedures (mean age of 67.9±9.7 years, 71.9% male, 71.0% symptomatic) an ISR of ≥70% was detected in 5.7% after a median of 8.6 months (IQR: 3.4-17.3). After multiple regression analysis, leukocyte count after CAS-intervention (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.02-1.69; p = 0.036), as well as stent length and width were associated with the development of an ISR during follow-up (OR: 1.25, 95% CI: 1.05-1.65, p = 0.022 and OR: 0.28, 95% CI: 0.09-0.84, p = 0.010). CONCLUSIONS: The majority of ISR during long-term follow-up after CAS occur within the first year. ISR is associated with periinterventional inflammation markers and influenced by certain stent characteristics such as stent length and width. Our findings support the assumption that stent geometry leading to vessel injury as well as periprocedural inflammation during CAS plays a pivotal role in the development of carotid artery ISR

Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism - the Find-AF 2 study - rationale and design

Background Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, i.e. ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. Methods Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. Conclusions The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care

Factors associated with time delay to carotid stenting in patients with a symptomatic carotid artery stenosis

Treatment of a symptomatic stenosis is known to be most beneficial within 14 days after the presenting event but this can frequently not be achieved in daily practice. The aim of this study was the assessment of factors responsible for this time delay to treatment. A retrospective analysis of a prospective two-center CAS database was carried out to investigate the potential factors that influence a delayed CAS treatment. Of 374 patients with a symptomatic carotid stenosis, 59.1% were treated beyond ≥14 days. A retinal TIA event (OR = 3.59, 95% CI 1.47–8.74, p < 0.01) was found to be a predictor for a delayed treatment, whereas the year of the intervention (OR = 0.32, 95% CI 0.20–0.50, p < 0.01) and a contralateral carotid occlusion (OR = 0.42, 95% CI 0.21–0.86, p = 0.02) were predictive of an early treatment. Similarly, within the subgroup of patients with transient symptoms, the year of the intervention (OR = 0.28, 95% CI 0.14–0.59, p < 0.01) was associated with an early treatment, whereas a retinal TIA as the qualifying event (OR = 6.96, 95% CI 2.37–20.47, p < 0.01) was associated with a delayed treatment. Treatment delay was most pronounced in patients with an amaurosis fugax, whereas a contralateral carotid occlusion led to an early intervention. Although CAS is increasingly performed faster in the last years, there is still scope for an even more accelerated treatment strategy, which might prevent future recurrent strokes prior to treatment

NfL (neurofilament light chain) levels as a predictive marker for long-term outcome after ischemic stroke

Background and Purpose Ischemic stroke causes major disability as a consequence of neuronal loss and recurrent ischemic events. Biomarkers predicting tissue damage or stroke recurrence might be useful to guide an individualized stroke therapy. NfL (neurofilament light chain) is a promising biomarker that might be used for this purpose. Methods We used individual data of patients with an acute ischemic stroke and clinical long term follow-up. Serum NfL (sNfL) was quantified within 24 hours after admission and after 1 year and compared with other biomarkers (GDF15 [growth differentiation factor 15], S100, NT-proBNP [N-terminal pro-B-type natriuretic peptide], ANP [atrial natriuretic peptide], and FABP [fatty acid–binding protein]). The primary end point was functional outcome after 90 days and cerebrovascular events and death (combined cardiovascular end point) within 36 months of follow-up. Results Two hundred eleven patients (mean age, 68.7 years; SD, ±12.6; 41.2% women) with median clinical severity on the National Institutes of Health Stroke Scale (NIHSS) score of 3 (interquartile range, 1–5) and long-term follow-up with a median of 41.8 months (interquartile range, 40.0–44.5) were prospectively included. We observed a significant correlation between sNfL and NIHSS at hospital admission (r=0.234; P<0.001). sNfL levels increased with the grade of age-related white matter changes (P<0.001) and were able to predict unfavorable clinical outcome (modified Rankin Scale score, ≥2) 90 days after stroke (odds ratio [OR], 1.562; 95% CI, 1.003–2.433; P=0.048) together with NIHSS (OR, 1.303; 95% CI, 1.164–1.458; P<0.001) and age-related white matter change rating (severe; OR, 3.326; 95% CI, 1.186–9.326; P=0.022). Similarly, sNfL was valuable for the prediction of the combined cardiovascular end point (OR, 2.002; 95% CI, 1.213–3.302; P=0.007), besides NIHSS (OR, 1.110; 95% CI, 1.000–1.232; P=0.049), diabetes mellitus (OR, 2.942; 95% CI, 1.306–6.630; P=0.005), and age-related white matter change rating (severe; OR, 4.816; 95% CI, 1.206–19.229; P=0.026) after multivariate regression analysis. Kaplan-Meier analysis revealed significantly more combined cardiovascular end points (18 [14.1%] versus 38 [45.8%], log-rank test P<0.001) during long-term follow-up in patients with elevated sNfL levels. Conclusions sNFL is a valuable biomarker for functional independence 90 days after ischemic stroke and predicts cardiovascular long-term outcome

Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke

Background and Purpose-Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods-Patients with acute cerebral ischemia >= 60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3x 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results-A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care (P=0.002). Median BNP was higher in patients with pAF as compared to patients without AF in both study arms at baseline (57.8 versus 28.3 pg/mL in the EPM arm, P=0.0003; 46.2 versus 27.7 pg/mL, P=0.28 in the control arm) and after 3 months (74.9 versus 31.3 pg/mL, P=0.012 in the EPM arm, 99.3 versus 26.3 pg/mL, P=0.02 in the control arm). Applying a cut off of 100 pg/mL, the number needed to screen was reduced from 18 by usual care to 3 by EPM. Conclusions-BNP measured early after ischemic stroke identifies a subgroup of patients with stroke at increased risk for AF, in whom EPM is particularly efficacious

Evaluation of coercive measures in different psychiatric hospitals: the impact of institutional characteristics

Background!#!Epidemiological studies have demonstrated considerable differences in the use of coercive measures among psychiatric hospitals; however, the underlying reasons for these differences are largely unclear. We investigated to what extent these differences could be explained by institutional factors.!##!Methods!#!Four psychiatric hospitals with identical responsibilities within the mental health care system, but with different inpatient care organizations, participated in this prospective observational study. We included all patients admitted over a period of 24 months who were affected by mechanical restraint, seclusion, or compulsory medication. In addition to the patterns of coercive measures, we investigated the effect of each hospital on the frequency of compulsory medication and the cumulative duration of mechanical restraint and seclusion, using multivariate binary logistic regression. To compare the two outcomes between hospitals, odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated.!##!Results!#!Altogether, coercive measures were applied in 1542 cases, corresponding to an overall prevalence of 8%. The frequency and patterns of the modalities of coercive measures were different between hospitals, and the differences could be at least partially related to institutional characteristics. For the two hospitals that had no permanently locked wards, certain findings were particularly noticeable. In one of these hospitals, the probability of receiving compulsory medication was significantly higher compared with the other institutions (OR 1.9, CI 1.1-3.0 for patients &amp;lt; 65 years; OR 8.0, CI 3.1-20.7 for patients ≥65 years); in the other hospital, in patients younger than 65 years, the cumulative duration of restraint and seclusion was significantly longer compared with the other institutions (OR 2.6, CI 1.7-3.9).!##!Conclusions!#!The findings are compatible with the hypothesis that more open settings are associated with a more extensive use of coercion. However, due to numerous influencing factors, these results should be interpreted with caution. In view of the relevance of this issue, further research is needed for a deeper understanding of the reasons underlying the differences among hospitals

Periprocedural variables.

<p>pre = preprocedural (within 24 hours before CAS), post = postprocedural (within 24 hours after CAS), CRP = C-reactive protein.</p><p>*factors included into multiple regression analysis.</p>†<p>factors remained significant after multiple regression analysis.</p