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, ie, 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.

Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A Subanalysis of the Find-AFRANDOMISED Trial.

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 (3× 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. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01855035.

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. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN 46104198.

Added value of CT perfusion compared to CT angiography in predicting clinical outcomes of stroke patients treated with mechanical thrombectomy.

OBJECTIVES: CTP images analyzed with the Alberta stroke program early CT scale (ASPECTS) have been shown to be optimal predictors of clinical outcome. In this study we compared two biomarkers, the cerebral blood volume (CBV)-ASPECTS and the CTA-ASPECTS as predictors of clinical outcome after thrombectomy. METHODS: Stroke patients with thrombosis of the M1 segment of the middle cerebral artery were included in our study. All patients underwent initial multimodal CT with CTP and CTA on a modern CT scanner. Treatment consisted of full dose intravenous tissue plasminogen activator, when applicable, and mechanical thrombectomy. Three neuroradiologists separately scored CTP and CTA images with the ASPECTS score. RESULTS: Sixty-five patients were included. Median baseline CBV-ASPECTS and CTA-ASPECTS for patients with favourable clinical outcome at follow-up were 8 [interquartile range (IQR) 8-9 and 7-9 respectively]. Patients with poor clinical outcome showed a median baseline CBV-ASPECTS of 6 (IQR 5-8, P < 0.0001) and a median baseline CTA-ASPECTS of 7 (IQR 7-8, P = 0.18). Using CBV-ASPECTS and CTA-ASPECTS raters predicted futile reperfusions in 96 % and 56 % of the cases, respectively. CONCLUSIONS: CBV-ASPECTS is a significant predictor of clinical outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. KEY POINTS: • CBV-ASPECTS is a significant predictor of clinical outcome. • Single phase CTA-ASPECTS has low predictive value. • Using CBV-ASPECTS, raters identified futile reperfusions in 96 % of the cases.

Time-resolved assessment of collateral flow using 4D CT angiography in large-vessel occlusion stroke.

OBJECTIVES: In acute stroke patients with large vessel occlusion, collateral blood flow affects tissue fate and patient outcome. The visibility of collaterals on computed tomography angiography (CTA) strongly depends on the acquisition phase, but the optimal time point for collateral imaging is unknown. METHODS: We analysed collaterals in a time-resolved fashion using four-dimensional (4D) CTA in 82 endovascularly treated stroke patients, aiming to determine which acquisition phase best depicts collaterals and predicts outcome. Early, peak and late phases as well as temporally fused maximum intensity projections (tMIP) were graded using a semiquantitative regional leptomeningeal collateral score, compared with conventional single-phase CTA and correlated with functional outcome. RESULTS: The total extent of collateral flow was best visualised on tMIP. Collateral scores were significantly lower on early and peak phase as well as on single-phase CTA. Collateral grade was associated with favourable functional outcome and the strength of this relationship increased from earlier to later phases, with collaterals on tMIP showing the strongest correlation with outcome. CONCLUSIONS: Temporally fused tMIP images provide the best depiction of collateral flow. Our findings suggest that the total extent of collateral flow, rather than the velocity of collateral filling, best predicts clinical outcome. KEY POINTS: • Collateral flow visibility on CTA strongly depends on the acquisition phase • tMIP offers the best visualisation of the extent of collaterals • Outcome prediction may be better with tMIP than with earlier phases.• Total extent of collaterals seems more important than their filling speed • If triggered too early, CTA may underestimate collateral flow.

Symmetric Dimethylarginine Predicts Previously Undetected Atrial Fibrillation in Patients With Ischemic Stroke.

BACKGROUND: Atrial fibrillation (AF) is a stroke risk factor that often remains undetected at hospital admission. Long-term Holter monitoring helps to identify patients with previously unrecognized AF. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are elevated in AF in cross-sectional studies. We analyzed ADMA, SDMA, and other L-arginine metabolites to assess their association with AF in the Find-AF trial. METHODS AND RESULTS: We included 280 patients presenting with acute cerebral ischemia. Patients presenting in sinus rhythm received 7-day Holter-ECG. Biomarkers were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. We also analyzed protein methylation and L-arginine-related metabolites in human induced pluripotent stem cell-derived cardiomyocytes in vitro. ADMA and SDMA were elevated in 44 patients who presented with AF. SDMA, but not ADMA, was significantly elevated in patients newly diagnosed with AF in Holter-ECG as compared with those in sinus rhythm. SDMA plasma concentration >0.571 µmol/L significantly predicted presence of AF in Holter-ECG (area under the curve=0.676 [0.530-0.822]; P=0.029; sensitivity 0.786, specificity 0.572). SDMA levels further increased in patients with AF during the first 24 hours in hospital, and ADMA levels remained stable. In vitro, induced pluripotent stem cell-derived cardiomyocytes showed increased symmetric protein methylation and elevated SDMA during rapid pacing (2.0 Hz versus 0.5 Hz), whereas asymmetric protein methylation and ADMA were unchanged. CONCLUSIONS: SDMA at admission was significantly elevated in stroke patients presenting with AF and showed a moderate but significant prospective association with previously unrecognized AF. Thus, stroke patients with elevated SDMA concentration at admission may specifically benefit from extended Holter-ECG monitoring.

Alberta Stroke Program Early CT Scale evaluation of multimodal computed tomography in predicting clinical outcomes of stroke patients treated with aspiration thrombectomy.

BACKGROUND AND PURPOSE: Patient selection is crucial in the endovascular treatment of acute ischemic stroke patients. Baseline computed tomographic (CT) images, evaluated with the Alberta Stroke Program Early CT Scale (ASPECTS), are considered significant predictors of outcome. In this study, we evaluated CT images and perfusion parameters, analyzed with ASPECTS, as final outcome predictors after endovascular stroke treatment. METHODS: We analyzed a cohort of patients with acute ischemic stroke and endovascular treatment. Patients with an occlusion of the M1 segment and multimodal CT imaging were included. CT perfusion data were reconstructed using commercial software. Two experienced neuroradiologists separately reviewed and scored CT and CT perfusion images with the ASPECTS score. Parameters were compared between patients with poor and with favorable follow-up outcome. Significantly different variables were further analyzed by forward stepwise logistic regression. RESULTS: Fifty-one patients were included in our study. Baseline characteristics did not differ between patients with favorable and poor outcomes. No significant difference in recanalization status, the various times, or CT ASPECTS was demonstrated between these 2 groups. Significant differences were demonstrated for age (P=0.0049), cerebral blood volume ASPECTS (P=0.0007), and between cerebral blood volume and cerebral blood flow ASPECTS (P=0.0045). Cerebral blood volume ASPECTS>7 demonstrated the highest sensitivity and specificity for favorable outcome with 84% and 79%, respectively. CONCLUSIONS: CT perfusion parameters, evaluated with ASPECTS, are optimal predictors of outcome and are more sensitive and specific than CT ASPECTS in the prediction of favorable outcome. Use of these parameters in treatment decisions could reduce futile recanalizations.

High-sensitivity troponin assay improves prediction of cardiovascular risk in patients with cerebral ischaemia.

BACKGROUND AND PURPOSE: Clinical scores are recommended for predicting cardiovascular risk in patients with cerebral ischaemia to inform secondary prevention. Blood biomarkers may improve prediction beyond clinical scores. METHODS: Within the observational Find-AF trial (ISRCTN46104198), 197 patients >18 years of age with cerebral ischaemia and without atrial fibrillation had blood sampled at baseline. The predictive value of five biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to the Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2) and National Institutes of Health Stroke Scale (NIH-SS). RESULTS: There were 23 vascular events (11.7%) and 13 deaths (6.6%) to 1 year follow-up. In multivariate analyses of all markers, only high-sensitivity troponin T (hsTropT) remained independently predictive for vascular events (p=0.045) and all-cause mortality (p=0.004). hsTropT was higher in patients with a vascular event (median 12.7 ng/ml vs 5.1 ng/ml), and patients with hsTropT above the median of 6.15 ng/ml had vascular events more frequently (HR 3.86, p=0.008). For prediction of vascular events as well as all-cause mortality, hsTropT significantly improved multivariate Cox regression models with ESRS, SPI-2 or NIH-SS. The c-statistic increased non-significantly from 0.695 (ESRS) or 0.710 (hsTropT) to 0.747 (ESRS+hsTropT) and from 0.699 (SPI-2) to 0.763 (SPI-2+hsTropT). No patient with a low-risk ESRS and an hsTropT below the median had a vascular event or died. CONCLUSIONS: hsTropT predicts vascular events and all-cause mortality in patients with acute cerebral ischaemia and improves prediction beyond established clinical scores.

Plaque morphology detected with Duplex ultrasound before carotid angioplasty and stenting (CAS) is not a predictor of carotid artery in-stent restenosis, a case control study.

BACKGROUND: In-stent restenosis (ISR) is an important factor endangering the long-term safety and efficacy of carotid artery angioplasty and stenting (CAS). It is plausible that soft vulnerable plaques are more likely to be injured during CAS procedure and are therefore more likely to initiate the cascade finally leading to ISR. The aim of this study was to investigate if plaque morphology detected by a simple applicable Duplex ultrasound score before CAS can be used as a predictor for ISR. METHODS: Within a prospectively collected single-centre CAS database of 281 patients (comprising 300 arteries) with high-grade carotid artery stenosis, who underwent CAS between May 2003 and January 2013, we conducted a nested case-control study. Plaque morphology before CAS was analysed by a blinded investigator and each parameter of the Total Plaque Risk Score (TPRS) as well as the whole score was evaluated with regard to its diagnostic validity for ISR. RESULTS: We analysed the data of 10 patients with ISR and 50 patients without ISR. There were no significant differences with respect to baseline characteristics, vascular risk factors, and degree of stenosis between patients with and without ISR. The duration of follow-up was longer in patients with ISR (p = 0.024) and these patients were more likely to show increased PSV (p = 0.012) immediately after CAS than patients without ISR. Neither individual parameters of the TPRS score nor the score as a whole were suitable as a diagnostic test for ISR development. CONCLUSIONS: In the present study we could demonstrate that the non-contrast enhanced DUS of the pre-interventional plaque formation cannot be used as a predictor for the development of ISR. Evaluating a more sophisticated, but not routinely available approach e.g. by ultrasound based plaque perfusion imaging or CT based plaque analysis could be helpful in the future in order to assess the role of plaque morphology in the context of ISR development.

Impact of a new metal artefact reduction algorithm in the noninvasive follow-up of intracranial clips, coils, and stents with flat-panel angiographic CTA: initial results.

INTRODUCTION: Flat-panel angiographic CT after intravenous contrast agent application (ivACT) is increasingly used as a follow-up examination after coiling, clipping, or stenting. The purpose of this study was to evaluate the feasibility of a new metal artefact reduction algorithm (MARA) in patients treated for intracranial aneurysms and stenosis. METHODS: IvACT was performed on a flat-panel detector angiography system after intravenous application of 80 ml contrast media. The uncorrected raw images were transferred to a prototype reconstruction workstation where the MARA was applied. Two experienced neuroradiologists examined the corrected and uncorrected images on a commercially available workstation. RESULTS: Artefacts around the implants were detected in all 16 uncorrected cases, while eight cases showed remaining artefacts after correction with the MARA. In the cases without correction, there were 11 cases with "extensive" artefacts and five cases with "many" artefacts. After correction, seven cases showed "few" and only one case "many" artefacts (Wilcoxon test, P < 0.001). Parent vessels were characterized as "not identifiable" in 62% of uncorrected images, while the delineation of parent vessels were classified as "excellent" in 50% of the cases after correction (Wilcoxon test, P = 0.001). CONCLUSIONS: Use of the MARA in our study significantly reduced artefacts around metallic implants on ivACT images and allowed for the delineation of surrounding structures.

Long-Term Follow-up of Enhanced Holter-Electrocardiography Monitoring in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk. METHODS: We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months. RESULTS: Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37). CONCLUSIONS: Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.

New brain lesions after carotid revascularization are not associated with cognitive performance.

PURPOSE: Carotid angioplasty and stenting (CAS) is increasingly being used as a treatment alternative to endarterectomy (CEA) for patients with significant carotid stenosis. However, diffusion-weighted imaging (DWI) has indicated that CAS is associated with a significantly higher burden of microemboli. This study evaluated the potential effect on intellectual functions of new DWI lesions after CEA or CAS. METHODS: This prospective study analyzed the neuropsychologic outcomes after revascularization in 24 CAS and 31 CEA patients with severe carotid stenosis compared with a control group of 27 healthy individuals. All patients underwent clinical examinations, magnetic resonance imaging scans, and a neuropsychologic test battery that assessed six major cognitive domains performed immediately before CEA or CAS, ≤ 72 hours after, and at 3 months. RESULTS: New DWI lesions were detected among 15 of 21 (71%) of the CAS patients immediately after treatment but in only 1 of the 28 CEA patients (4%; P < .01). As a group, patients with new DWI lesions showed a decline in their performance in the cognitive domains, attention, and visuoconstructive functions within 72 hours of carotid revascularization. Individually, however, in none of the cognitive domains did the decreases reach a clinically relevant threshold of z < -1.5. Moreover, the cognitive performance was not significantly different between patients with and without new DWI lesions 3 months after treatment. The cognitive performance was similar between CEA and CAS patients at all points. CONCLUSIONS: The findings support the assumption that new brain lesions, as detected with DWI after CAS or CEA, do not affect cognitive performance in a manner that is long-lasting or clinically relevant. Despite the higher embolic load detected by DWI, CAS is not associated with a greater cognitive decline than CEA.

Health-related quality of life, anxiety and depression up to 12 months post-stroke: Influence of sex, age, stroke severity and atrial fibrillation - A longitudinal subanalysis of the Find-AFRANDOMISED trial.

BACKGROUND: Stroke can negatively impact the health-related quality of life (HRQoL). Anxiety or depression after stroke have been associated with poorer HRQoL, higher mortality and greater dependence in activities of daily living. We aimed to analyze HRQoL, anxiety and depressive symptoms in patients with and without atrial fibrillation (AF) up to 12 months post-stroke. METHODS: Find-AFRANDOMISED was a prospective, randomized multicenter study, which included 398 patients ≥60 years with acute cerebral ischemia. HRQoL data were collected using the 3-level EuroQol-5D (EQ-5D-3L) and Stroke Impact Scale (SIS-16). Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). The severity of stroke was measured using the modified Rankin Scale (mRS). RESULTS: In this study (mean age 72.7 ± 7.5 years, 40.2% females), there was a significant improvement in HRQoL using EQ-5D-3L after 3 months (ß = 0.37, p < .01), 6 months (ß = 0.43, p < .01) and 12 months (ß = 0.44, p < .01) post-stroke compared to baseline. HADS anxiety scores after 3 months (ß = -0.22, p < .01) and 12 months (ß = -0.28, p < .01) were significantly reduced. Older patients reported reduced HRQoL and more depressive symptoms. Females indicated lower HRQoL and more anxiety. mRS score at baseline was an independent predictor for HRQoL. There was a significant but small effect of AF on EQ-5D-3L and on HADS anxiety. CONCLUSIONS: Patients showed significant improvement in HRQoL and reduced anxiety after 3 and 12 months after stroke. We could demonstrate that the severity of stroke as well as sex and age impact long-term post-stroke HRQoL. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01855035.

Software-based analysis of 1-hour Holter ECG to select for prolonged ECG monitoring after stroke.

OBJECTIVE: Identification of ischemic stroke patients at high risk for paroxysmal atrial fibrillation (pAF) during 72 hours Holter ECG might be useful to individualize the allocation of prolonged ECG monitoring times, currently not routinely applied in clinical practice. METHODS: In a prospective multicenter study, the first analysable hour of raw ECG data from prolonged 72 hours Holter ECG monitoring in 1031 patients with acute ischemic stroke/TIA presenting in sinus rhythm was classified by an automated software (AA) into "no risk of AF" or "risk of AF" and compared to clinical variables to predict AF during 72 hours Holter-ECG. RESULTS: pAF was diagnosed in 54 patients (5.2%; mean age: 78 years; female 56%) and was more frequently detected after 72 hours in patients classified by AA as "risk of AF" (n = 21, 17.8%) compared to "no risk of AF" (n = 33, 3.6%). AA-based risk stratification as "risk of AF" remained in the prediction model for pAF detection during 72 hours Holter ECG (OR3.814, 95% CI 2.024-7.816, P < 0.001), in addition to age (OR1.052, 95% CI 1.021-1.084, P = 0.001), NIHSS (OR 1.087, 95% CI 1.023-1.154, P = 0.007) and prior treatment with thrombolysis (OR2.639, 95% CI 1.313-5.306, P = 0.006). Similarly, risk stratification by AA significantly increased the area under the receiver operating characteristic curve (AUC) for prediction of pAF detection compared to a purely clinical risk score (AS5F alone: AUC 0.751; 95% CI 0.724-0.778; AUC for the combination: 0.789, 95% CI 0.763-0.814; difference between the AUC P = 0.022). INTERPRETATION: Automated software-based ECG risk stratification selects patients with high risk of AF during 72 hours Holter ECG and adds predictive value to common clinical risk factors for AF prediction.

A systematic review on outcome after stenting for intracranial atherosclerosis.

BACKGROUND AND PURPOSE: Angioplasty and stenting is increasingly being used for the treatment of intracranial stenoses. Based on a literature search (01/1998 to 04/2008) we sought to determine the immediate and long-term outcomes, as well as the durability of this procedure. SUMMARY OF REVIEW: We identified 31 studies dealing with 1177 procedures, which had mainly been performed in patients with a symptomatic (98%) intracranial high-grade stenosis (mean: 78+/-7%) at high technical success rates (median: 96%; interquartile range [IQR]: 90% to 100%). The periprocedural minor or major stroke and death rates ranged from 0% to 50% with a median of 7.7% (IQR: 4.4% to 14.3%). Periprocedural complications were significantly higher in the posterior versus the anterior circulation (12.1%, versus 6.6%, P<0.01, odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.21 to 3.10), but did not differ between patients treated with a balloon-mounted (n=906) versus those who had been treated with a self-expandable stent (n=271; 9.5% versus 7.7%, P=0.47, OR: 1.15, CI:0.76 to 2.05). Restenosis >50% occurred more frequently after the use of a self-expandable stent (16/92; 17.4%, mean follow-up time: 5.4 months) than a balloon-mounted stent (61/443; 13.8%, mean follow-up time: 8.7 months; P<0.001, log-rank test). CONCLUSIONS: Although intracranial stenting appears to be feasible, adverse events vary widely. Against the background of the results of this review yielding a high rate of restenoses and no clear impact of new stent devices on outcome, the widespread application of intracranial stenting outside the setting of randomized trials and in inexperienced centers currently does not seem to be justified.

The cardiac diagnostic work-up in stroke patients-A subanalysis of the Find-AFRANDOMISED trial.

BACKGROUND: The cardiac diagnostic workup of stroke patients, especially the value of echocardiography and enhanced and prolonged Holter-ECG monitoring, is still a matter of debate. We aimed to analyse the impact of pathologies detected by echocardiography and ECG monitoring on therapeutic decisions and prognosis. METHODS: Find-AFRANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to enhanced and prolonged Holter-ECG monitoring or usual stroke unit care. This substudy compared therapeutic consequences of echocardiography and routine Holter-ECG or enhanced and prolonged Holter-ECG monitoring, respectively, and prognosis of patients with or without pathologic findings in echocardiography or Holter-ECG monitoring. RESULTS: 50.3% received enhanced and prolonged Holter-ECG monitoring and 49.7% routine ECG monitoring. 82.9% underwent transthoracic echocardiography (TTE), 38.9% transesophageal echocardiography (TEE) and 25.6% both procedures. 14/89 TEE pathologies and 1/90 TTE pathology led to a change in therapy, resulting in a number needed to change decision (NNCD) of 12 and 330 (p < 0.001), respectively. In comparison, enhanced and prolonged Holter-ECG monitoring found atrial fibrillation (AF) in 27 of 200 patients, and routine ECG monitoring in twelve of 198 patients, leading to therapeutic changes in all patients (NNCD 8 and 17, respectively, p < 0.001). CONCLUSIONS: Most changes in therapeutic decisions were triggered by enhanced and prolonged Holter-ECG monitoring, which should therefore play a more prominent role in future guidelines. Echocardiography identifies a patient group at high cardiovascular risk, but rarely result in therapeutic changes. Whether this patient group requires further cardiovascular workup remains unknown. This should be further investigated by interdisciplinary neurocardiologic teams and in appropriate future trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01855035.

Carotid artery disease: stenting versus endarterectomy.

Atherosclerotic carotid artery stenosis is a major cause of disabling stroke or death. Although carotid endarterectomy (CEA) is currently considered to be the standard of care for patients with a severe symptomatic stenosis and selected patients with an asymptomatic carotid stenosis, carotid angioplasty and stenting (CAS) is increasingly being used as an alternative treatment modality. This article briefly summarizes the current trial data on CEA and CAS. More importantly, potential risk factors for CEA and CAS are reviewed and the complementary role of these techniques in the management of the individual patient is discussed.

A risk score to predict ischemic lesions after protected carotid artery stenting.

BACKGROUND AND PURPOSE: While carotid artery stenting can be performed safely in many patients, some have a higher risk for periprocedural complications. The detection of embolic lesions after CAS with DWI could become a useful means to identify these patients. The aim of this study was to determine risk factors for new DWI lesions after CAS. METHODS: One hundred seventy-six patients who had undergone protected CAS with pre- and postprocedural DWI between November 2000 and December 2006 were included in this retrospective investigation. The association of potential angiographic and clinical risk factors with the incidence of any new ipsilateral DWI lesion after CAS was analyzed with logistic regression analysis. Subsequently, a simple risk score was developed using area under the curve (ROC) statistics. RESULTS: The proportion of patients with any new ipsilateral DWI lesion was 51%. Advanced age (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.11, p=0.008), the presence of an ulcerated stenosis (OR 2.28: 95% CI 1.10-4.75; p=0.027) or a lesion length>1 cm (OR 2.65; 95% CI 1.33-5.28, p=0.006) were independent risk factors for new ipsilateral DWI lesions. A 4 point score ranging from 0 to 4 (age> or =70 years=1 point, age> or =80 years=2 points, lesion length>1 cm=1 point, and presence of an ulcerated stenosis=1 point) reliably predicted the incidence of this outcome parameter (ROC=0.70, p<0.001). CONCLUSIONS: A simple risk score can be used to identify patients at a high risk for new DWI lesions as a possible surrogate of embolic complications after CAS.

Bridging-therapy with intravenous recombinant tissue plasminogen activator improves functional outcome in patients with endovascular treatment in acute stroke.

BACKGROUND: Although endovascular treatment for proximal cerebral vessel occlusion is very effective, it remains controversial if intravenous thrombolysis (IVT) prior to endovascular treatment is superior compared to endovascular treatment alone. In this study we compared functional outcomes and recanalization rates of endovascularly treated stroke patients with and without bridging IVT. METHODS: Patients with acute large artery occlusion within the anterior and posterior cerebral circulation eligible for intraarterial revascularization with and without prior IVT were included in this monocentric, prospective observational study. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) were determined at baseline, discharge and 90-days follow up after stroke. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3. RESULTS: Of the 109 patients included, 81 (74%) received bridging therapy with i.v.-rtPA prior to endovascular treatment, 28 (26%) received endovascular treatment alone. There was no difference in groin-to-reperfusion time between the groups (54 vs 50min; p=0.657), but a trend towards a higher reperfusion rate in patients with bridging therapy (69 vs 15 patients, p=0.099). Mean improvement of the NIHSS during hospitalization was 8 points (SD; ±8) in the bridging-group and 2 points (SD, ±7) in the non-bridging-group (p=0.001). Number of patients with discharge mRS 0-2 (34 vs 5; p=0.024) and 90-days mRS 0-2 (35 vs 6; p=0.061) was higher in the bridging-group compared to the non-bridging-group. CONCLUSIONS: This study provides evidence that bridging therapy with i.v.-rtPA improves functional outcome in patients eligible for endovascular treatment. Further studies are needed to confirm our findings and to identify patients most likely benefitting from bridging therapy.

Relevance of supraventricular runs detected after cerebral ischemia.

OBJECTIVE: Prolonged ECG monitoring after stroke frequently reveals short paroxysmal atrial fibrillation (pAF) and supraventricular (SV) runs. The minimal duration of atrial fibrillation (AF) required to induce cardioembolism, the relevance of SV runs, and whether short pAF results from cerebral damage itself are currently being debated. We aimed to study the relevance of SV runs and short pAF detected by prolonged Holter ECG after cerebral ischemia during long-term follow-up. METHODS: Analysis is from the prospective Find-AF trial (ISRCTN46104198). We included patients with acute cerebral ischemia. Those without AF on admission received 7-day Holter ECG monitoring. We differentiated patients with AF on admission (AF-adm), with pAF (>30 seconds), with SV runs (>5 beats but <30 seconds in a 24-hour ECG interval), and without SV runs (controls). During follow-up, those with baseline pAF received another 7-day Holter ECG to examine AF persistence. RESULTS: A total of 254 of 281 initially included patients were analyzed (mean age 70.0 years, 45.3% female). Forty-three (16.9%) had AF-adm. A total of 211 received 7-day Holter ECG monitoring: 27 (12.8%) had pAF, 67 (31.8%) had SV runs, and 117 (55.5%) were controls. During a mean 3.7 years of follow-up, the SV runs group had more recurrent strokes (p = 0.04) and showed numerically more novel AF (12% vs 5%, p = 0.09) than the controls. Seventy-five percent of the patients with manifest pAF detected after cerebral ischemia still had AF during follow-up (50% paroxysmal, 50% persisting/permanent). CONCLUSIONS: Patients with cerebral ischemia and SV runs had more recurrent strokes and numerically more novel AF during follow-up and could benefit from further prolonged ECG monitoring. pAF detected after stroke is not a temporal phenomenon.