Search

Background and Purpose: Tandem lesions in the anterior circulation account for up to 30% of all large vessel occlusion strokes. The optimal periprocedural approach in these lesions is still a matter of debate. Methods: Data from the German Stroke Registry—Endovascular Treatment between June 2015 and December 2019 were analyzed. The German Stroke Registry—Endovascular Treatment is an academic, independent, prospective, multicenter, observational registry study with 25 participating stroke centers from all over Germany enrolling consecutive mechanical thrombectomy patients. Tandem lesions were defined as a combination of a relevant extracranial internal carotid artery (ICA) pathology (ipsilateral stenosis >70% or occlusion) and concomitant intracranial large vessel occlusion. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b-3. The modified Rankin Scale score of 0 to 2 at 3 months indicated good outcome. The aim of this study was to investigate the safety and efficacy of different technical strategies in tandem lesions. Results: Out of 6635 patients, 874 (13.2%) presented with tandem lesions. Of these, 607 (69.5%) underwent acute treatment of the extracranial ICA. Acute treatment of the extracranial ICA lesion led to a higher probability of successful reperfusion (odds ratio, 40.63 [95% CI, 30.03–70.06]) compared with patients who did not undergo acute treatment of the extracranial ICA lesion and was associated with good clinical outcome (39.5% versus 29.3%, P P P =0.035) and intravenous thrombolysis (odds ratio, 10.58 [95% CI, 10.04–20.4]; P =0.033). Intracranial-first approach (n=227) compared with extracranial-first approach (n=267) resulted in a shorter time to flow restoration (53.5 versus 72.0 minutes, P P =0.24) without differences in periprocedural complications. Conclusions: In tandem lesions in the anterior circulation, acute treatment of the extracranial ICA lesion is associated with better clinical outcome and lower mortality. The intracranial-first approach might provide advantages.

Introduction Previous studies showed insufficient control of cardiovascular risk factors (CVRF) and high stroke recurrence rates among ischemic stroke patients in Germany. Currently, no structured secondary prevention program exists in clinical routine. We present the trial design and pilot phase results of a complex intervention to improve stroke care after hospital discharge in Germany. Patients and methods SANO is a cluster-randomized trial with 30 participating regions across Germany aiming to enrol 2,790 patients (drks.de, DRKS00015322). Study intervention combines both structural and patient-centred elements. Study development was based on the Medical Research Council framework for complex interventions. In 15 intervention regions, a cross-sectoral multidisciplinary network is established to enhance CVRF control as well as detection and treatment of post-stroke complications. Recommendations on CVRF are based on high-quality secondary prevention guidelines. Study physicians use motivational interviewing and agree with patients on therapeutic targets. While hospitalised, patients also receive dietary counselling and a health-passport to track their progress. During regular visits, CVRF management and potential complications are monitored. The intervention is compared to 15 regions providing usual care. The primary endpoint is the combination of recurrent stroke, myocardial infarction and death assessed 12 months after enrolment and adjudicated in a blinded manner. Results Eighteen patients were enrolled in a pilot phase that demonstrated feasibility of patient recruitment and study procedures. Conclusion SANO is investigating a program to reduce outcome events after ischemic stroke by implementing a complex intervention. If successful, the program may be implemented in routine care on national level in Germany.

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.

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 P P =0.048) together with NIHSS (OR, 1.303; 95% CI, 1.164–1.458; P 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 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.

ZusammenfassungNeurovaskuläre Erkrankungen gehören zu den häufigsten Erkrankungen im neurologischen Fachgebiet. Vor dem Hintergrund der immer älter werdenden Gesellschaft spielt der Schlaganfall und damit dessen Diagnostik eine herausragende Rolle. Für den Neurologen in eigener Hand ermöglicht der Ultraschall nicht nur die Einschätzung der Gefäßsituation in der Primärprophylaxe, sondern selbstverständlich v. a. beim akuten Schlaganfall bei Beantwortung der Fragestellung hinsichtlich einer Thrombektomie oder Thrombolyse. Auch im Verlauf hilft der Ultraschall bei der ätiologischen Zuordnung und somit wichtige Therapieentscheidungen zu treffen. Hier sind neben arteriosklerotischen Obstruktionen insbesondere Dissektionen zu nennen. In der Zukunft wird aufgrund der neuen Studienlage pro invasiver Therapie auch die sonografische Detektion eines kardialen Rechts-Links-Shunts mittels transkranieller Doppler- oder Duplexsonografie von noch größerer Bedeutung sein. Nach therapeutischen Eingriffen insbesondere an der extrakraniellen Arteria carotis interna wird die Sonografie zur Beurteilung des Operations- oder Interventionsergebnisses und bei der Verlaufskontrolle genutzt. Ebenso gelingt mit dem Ultraschall auch die Verlaufsbeurteilung intrakranieller Stenosen. Wertvoll ist der transkranielle Ultraschall auch in der Diagnostik auf der Intensivstation, bspw. zur Detektion erhöhten Hirndrucks oder in der Hirntoddiagnostik. Andere Anwendungen sind bspw. die Detektion von intrakraniellen Vasospasmen nach Subarachnoidalblutungen, die Diagnostik von Vaskulitiden der hirnversorgenden Gefäße, und neuerdings auch der transorbitale Ultraschall bei ischämischen Ophthalmopathien. Therapeutisch wird der Ultraschall in der Neurologie bisher überwiegend auf wissenschaftlicher Basis im Rahmen von Studien zur Sonothrombolyse eingesetzt. Die Anwendung transkranieller Sonografie zeigte beim akuten Mediaverschluss eine höhere Rekanalisationsrate, es kam allerdings auch zu etwas häufigeren, statistisch nicht signifikanten symptomatischen Einblutungen. In den meisten Fällen ist bei der alltäglichen Anwendung der Duplexsonografie der Vorzug zu geben, aber auch die einfache Dopplersonografie gehört nach wie vor zum Standardrepertoire der meisten Ultraschallabore. In diesem Artikel möchten wir Ihnen über die wichtigsten Anwendungen des Ultraschalls in der Neurologie einen Überblick geben.

Background and Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort. Methods: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0–2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders. Results: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0–10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7–7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8–5.6]). Conclusions: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03356392.

Summary Background Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. Methods In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov , NCT02204267 , and is completed and closed for participants. Findings Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9–1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0–2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8–1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5–0·9]). Interpretation Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. Funding Bayer Vital. Translation For the German translation of the abstract see Supplementary Materials section.

Background: The COVID-19 pandemic might affect health care resources and alter patient admission to hospital in case of stroke or transient ischemic attack (TIA). We aim to determine whether the COVID-19 pandemic is affecting utilization of recanalization procedures and numbers of patients with stroke and TIA admitted to a primary care stroke center.Methods: In this retrospective observational study, we compared patients admitted from January 2019 until February 2020 with patients admitted during the COVID-19 pandemic (March/April 2020) in Germany. We included patients with stroke (hemorrhagic or ischemic) or TIA as classified by International Statistical Classification of Diseases and Related Health Problems version 10 (ICD-10).Results: The number of patients per month with ischemic stroke or TIA was found to have significantly decreased from January 2019 until February 2020 compared to the COVID-19 pandemic (March/April 2020) (ischemic stroke 69.1 ± 4.5 vs. 55 ± 5.7, p < 0.001, TIA 22.1 ± 4.1 vs. 14.5 ± 6.4, p < 0.034). Contrarily, percentages and numbers of recanalization procedures per month were not influenced by the COVID-19 pandemic (intravenous thrombolysis [iv-tPA] 9.4 ± 3.7 vs. 10.5 ± 0.5, p = 0.697, mechanical thrombectomy [MT] 13.1 ± 3.1 vs. 14.5 ± 3.5, p = 0.580, iv-TPA or MT 19.4 ± 4.1 vs. 19.0 ± 0.0, p = 0.889).Conclusions: During the COVID-19 pandemic, resources of the healthcare system in a primary care university hospital in Germany still allowed for unchanged numbers of recanalization procedures due to ischemic stroke. However, the numbers of patients admitted to the hospital specifically due to ischemic stroke or TIA decreased, suggesting that the awareness for non-disabling stroke symptoms has to be increased.

Patients with stroke or transient ischemic attacks (TIAs) and internal carotid artery stenosis harbor an increased risk of recurrent stroke especially within 2 weeks after the first event. In addition, the revascularization procedure itself (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) is associated with both clinically apparent and silent brain infarctions, mainly caused by the embolic nature of the ruptured carotid plaque. The glycoprotein VI (GPVI) fusion protein Revacept is a highly specific antithrombotic drug without direct inhibition of systemic platelet function that might reduce periprocedural distal embolization from the vulnerable ruptured plaque located at the internal carotid artery. By shielding collagen at the site of vascular injury, Revacept inhibits plaque-mediated platelet adhesion and aggregation, while not directly affecting systemic hemostasis. In this phase II study, 158 patients with symptomatic carotid artery stenosis with recent TIA or stroke were randomized to receive a single dose of either Revacept (40 or 120 mg) or placebo. All patients were on standard secondary preventive therapy (statins and platelet inhibition) and underwent CEA, CAS, or best medical therapy according to current guidelines. The efficacy of Revacept was evaluated by exploratory assessment of new diffusion-weighted imaging lesions on magnetic resonance imaging after the revascularization procedure; a combination of cardiovascular events (ischemic and hemorrhagic stroke, TIA, myocardial infarction, or coronary intervention) and bleeding complications served to assess clinically critical patients' outcome and safety. This exploratory phase II randomized, double-blind clinical trial provides valuable insights on the safety, tolerability, and efficacy of Revacept in patients with symptomatic carotid artery stenosis.

Background Patients aged ≥90 were excluded or under‐represented in past thrombectomy trials; thus, uncertainty remains whether treatment benefits can be expected regardless of age. This study investigates outcome and safety of thrombectomy in nonagenarians to improve decision making in a real‐world setting. Methods and Results All currently available data of patients aged ≥90 enrolled in the GSR‐ET (German Stroke Registry–Endovascular Treatment) were combined with a smaller cohort from 3 tertiary stroke centers. Baseline characteristics, procedural (Thrombolysis in Cerebral Infarction scale) and functional outcomes (modified Rankin Scale; mRS ), as well as complications (symptomatic intracranial hemorrhage, serious adverse events; SAEs) were analyzed. Good functional outcome was defined as mRS ≤3 at 90‐days. 203 patients with anterior circulation stroke and prestroke mRS ≤3 were included. The rate of successful recanalization (Thrombolysis in Cerebral Infarction scale ≥2b) was 75.9% (154/203). Good functional outcome ( mRS ≤3) was observed in 21.6% (41 of 193) at 90‐days. In‐hospital mortality was 27.1% (55 of 203) and increased significantly at 90 days to 48.9% (93 of 190; P CI , 1.01–3.70; P =0.046) and initial National Institute of Health Stroke Scale (adjusted odds ratio, 0.85; 95% CI , 0.76–0.97; P =0.014) as independent predictors for good outcome. Patients with successful recanalization had a significant ( P =0.001) shift of mRS distribution with higher rates of good functional outcomes (23.8% [34 of 143] versus 14.9% [7 of 47]) and lower mortality at 90‐days (46.8% [67 of 143] versus 55.3% [26 of 47]). Conclusions Despite high mortality and less frequent favorable outcome, our data suggest that thrombectomy is still effective and safe for nonagenarians. Decision making for thrombectomy in patients aged ≥90 should be based on a case‐by‐case basis with regard to initial National Institute of Health Stroke Scale and Alberta Stroke Program Early CT Score.

Dieser CME-Fortbildungsartikel soll einen strukturierten Untersuchungsgang der Doppler- und Duplexsonografie der hirnversorgenden Gefase vermitteln und dabei auf besondere Schwierigkeiten/Fallstricke hinweisen. Im Einzelnen werden Kriterien zur Stenosegraduierung, haufig auftretende Fehlermoglichkeiten sowie anatomische und methodische Besonderheiten dargestellt. This CME article presents a structured examination of duplex sonography of the brain-supplying arteries, especially focusing on difficulties and pitfalls. Criteria for stenosis grading and common mistakes as well as anatomical and methodical characteristics are described in detail.

Zusammenfassung Hintergrund Demografischer Wandel, Urbanisierung sowie eine zunehmende Spezialisierung der Akutversorgung von Schlaganfallpatienten erfordern eine Anpassung von Versorgungsstrukturen mit dem Ziel, auch Patienten in ländlichen Regionen leitliniengerecht behandeln zu können. Methodik Im Frühjahr 2016 wurde ein landesweites telemedizinisches Schlaganfallnetzwerk unter Einbeziehung aller 6 überregionalen Stroke Units im Land Rheinland-Pfalz etabliert. Die Zuständigkeit für den Konsildienst wechselt täglich zwischen den Kliniken und steht rund um die Uhr zur Verfügung. Alle Kriterien des OPS 8.98b werden erfüllt. Am Netzwerk teilnehmen können alle regionalen Stroke Units und Kliniken, die prädefinierte Kriterien erfüllen und nicht in regionaler Konkurrenz mit etablierten Stroke Units stehen. Ergebnisse Zu Projektbeginn am 01.04. 2016 nahmen 6 Kliniken teil, die alle eine regionale Stroke Unit unter internistischer Leitung besitzen. Innerhalb des ersten Jahres erfolgten 1568 telemedizinische Konsile. Die Diagnosen waren ischämische Infarkte (n = 802 Patienten; 51,2 %), intrazerebrale Blutungen (n = 46; 2,9%), transitorisch ischämische Attacken (TIA; n = 319; 20,4 %) und nicht vaskuläre Ursachen (sog. Stroke Mimics; n = 400; 25,5 %). Die Latenz zwischen Klinikaufnahme und Konsilbeginn betrug im Median 21 Minuten (Interquartilrange (IQR) 22 Minuten), die mediane Konsildauer lag bei 24 Minuten (IQR 22 Minuten). Bei den Patienten mit ischämischen Schlaganfällen betrug die Lyserate 12,5 % (n = 100). Eine mechanische Thrombektomie wurde nach Weiterverlegung in eines der Zentren bei 4,6 % (n = 37) der Patienten durchgeführt. Schlussfolgerung Die telemedizinische Netzwerkbildung ist geeignet, die landesweite Versorgung von Schlaganfallpatienten sicherzustellen. Weitere Analysen, insbesondere zum Outcome, werden benötigt.

ZusammenfassungVerkürzte Liegezeiten, wachsender administrativer Aufwand, eine zunehmende Komplexität in Diagnostik und Therapie und der wirtschaftliche Druck gehen mit einer Zunahme der Arbeitsdichte für Ärzte in neurologischen Kliniken einher. Eine zu hohe Arbeitsdichte kann die Behandlungsqualität beeinträchtigen und die Ausbildung von Assistenzärzten gefährden. In der Pflege, in psychiatrischen Kliniken und im Bereich der neurologischen Rehabilitation gibt es aktuell Ansätze, Mindestpersonalstandards einzuführen. Vor diesem Hintergrund plädieren die Autoren für:– die Einführung von Personaluntergrenzen für Ärzte in neurologischen Kliniken, aber auch für andere Berufsgruppen und andere medizinische Fächer– die Entwicklung eines Personalbemessungsinstruments, mit dessen Hilfe für jede Klinik ein angemessener Personalschlüssel festgelegt werden kann– eine Verbindlichkeit der Personalstandards einschließlich einer kompletten Gegenfinanzierung – realistische Übergangsfristen angesichts des aktuellen Ärztemangels

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 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.

Background and purpose Prolonged electrocardiogram (ECG) monitoring after ischaemic stroke increases the diagnostic yield of paroxysmal atrial fibrillation (pAF). In order to facilitate the additional workload involved in ECG analysis due to prolonged monitoring times, we investigated the effectiveness of pAF detection with an automated software algorithm (SA) in comparison to the routine staff-based analysis (RA) during standard stroke-unit care. Therefore, patients with acute ischaemic stroke or transitory ischaemic attack presenting with sinus rhythmus on the admission ECG and no history of atrial fibrillation were prospectively included. Methods A 24-h Holter ECG assessment was performed using either RA based on a computer-aided evaluation and subsequent review by a cardiologist or a commercially available automated SA. In the case of discordant results concerning the occurrence of pAF between the two methods, the data underwent an independent external rating. Results Of 809 prospectively enrolled patients, 580 patients fulfilled the inclusion criteria. pAF was ultimately diagnosed in 3.3% of the cohort (19 patients). SA and RA correctly diagnosed pAF in 17 patients resulting in a comparable diagnostic effectiveness of the analysis methods (sensitivity: SA 89.5% vs. RA 89.5%; specificity: SA 99.3% vs. RA 99.1%; κ, 0.686; P < 0.001; 95% confidence interval, 0.525–0.847). RA revealed clinically relevant ECG abnormalities in an additional seven patients. Conclusions Although it should not completely replace RA, SA-based evaluation of Holter ECG reaches a high diagnostic effectiveness for the detection of pAF and can be used for a rapid and resource-saving analysis of ECG data to deal with prolonged monitoring times.

Background and purpose The detection of paroxysmal atrial fibrillation (pAF) in patients presenting with ischaemic stroke shifts secondary stroke prevention to oral anticoagulation. In order to deal with the time- and resource-consuming manual analysis of prolonged electrocardiogram (ECG)-monitoring data, we investigated the effectiveness of pAF detection with an automated algorithm (AA) in comparison to a manual analysis with software support within the IDEAS study [study analysis (SA)]. Methods We used the dataset of the prospective IDEAS cohort of patients with acute ischaemic stroke/transient ischaemic attack presenting in sinus rhythm undergoing prolonged 72-h Holter ECG with central adjudication of atrial fibrillation (AF). This adjudicated diagnosis of AF was compared with a commercially available AA. Discordant results with respect to the diagnosis of pAF were resolved by an additional cardiological reference confirmation. Results Paroxysmal AF was finally diagnosed in 62 patients (5.9%) in the cohort (n = 1043). AA more often diagnosed pAF (n = 60, 5.8%) as compared with SA (n = 47, 4.5%). Due to a high sensitivity (96.8%) and negative predictive value (99.8%), AA was able to identify patients without pAF, whereas abnormal findings in AA required manual review (specificity 96%; positive predictive value 60.6%). SA exhibited a lower sensitivity (75.8%) and negative predictive value (98.5%), and showed a specificity and positive predictive value of 100%. Agreement between the two methods classified by kappa coefficient was moderate (0.591). Conclusion Automated determination of 'absence of pAF' could be used to reduce the manual review workload associated with review of prolonged Holter ECG recordings.

Summary Background S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov , NCT02877615 . Findings Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding Servier.

Background: Detecting concealed paroxysmal atrial fibrillation (pAF) is a major focus of the workup of ischemic-stroke-patients, but requires elaborate ECG-monitoring. We aimed to evaluate pre-specified predictors to determine stroke patients with an increased probability of underlying pAF. We applied cut-off-levels recently suggested by the German Stroke Society 1 . Methods: The Find-AF RANDOMISED -trial (NCT01855035) evaluated 3x10-day Holter-ECG vs. standard-care in 398 patients > 60 years with acute ischemic strokes. The primary endpoint was novel pAF after 6 months. 27 patients in the intervention arm (13.5 %) and 9 patients in the control arm (9.0 %) met the primary endpoint (p=0.002). We used Pearson’s Chi 2 -test and the Mann-Whitney-U-test, as applicable. In variables with p Results: Table 1 shows known pAF-risk-factors in relation to whether patients had pAF. The absence of a clinical lacunar syndrome (p=0.007) or lacunar lesions (p=0.018), increased NIHSS-Score (p=0.003), frequent atrial premature beats (APB, p=0.003), prolonged supraventricular runs (p=0.01), enlarged left atria (p=0.07) and increased brain-natriuretic-peptide-levels (p=0.001) were associated with underlying pAF. Frequent APB differentiated best between those with and without pAF (area under the curve, AUC: 0.71). Conclusions: Several of the evaluated markers are useful to preselect stroke patients for enhanced ECG-monitoring. APB and comprehensive measures of both left atrial size and function (LAVI/a’) showed the highest AUC and should be used when preselecting stroke patients for prolonged ECG-monitoring.

Introduction: Serum neurofilament light chains (sNFL) are a marker of axonal injury in various neurologic diseases. We aimed to address their diagnostic and prognostic value in patients following acute ischemic stroke. Methods: We selected patients from the Find-AF trial (ISRCTN 46104198) with available serum samples 24 h after hospital admission and further brain imaging (MRI or CT-Scans with minimum 3 days after symptom onset). sNFL levels were measured using the SIMOA technique. Infarct size on brain imaging was classified as lacunar (< 10 cm 3 ) or non-lacunar (>10 cm 3 ). We assessed whether sNFL was associated with: (I) clinical severity on admission (II) lesion volume in brain imaging and (III) functional outcome after 3 and 12 months. Results: 58 patients fulfilled the inclusion criteria with a median age of 73 years (IQR 61-79), median NIHSS at baseline of 4 (IQR 2-8) and median modified Rankin Scale (mRS) at baseline of 3 (IQR 2-4). Among patients with acute ischemic stroke, sNFL levels were not associated with clinical severity (measured by NIHSS and mRS; p = 0.83 and p = 0.43, respectively) or lesion size in brain imaging at baseline (lacunar 80.3 pg/ml, non-lacunar 122.9 pg/ml, p = 0.16). Nevertheless, baseline sNFL levels correlated with functional outcome as measured by mRS after 90 days: mRS ≤ 2, 75.9 pg/ml; mRS > 2, 110.8 pg/ml; p = 0.018. This prognostic ability of sNFL was preserved for functional outcome measurements after 12 month: mRS ≤ 1, 71.3 pg/ml; mRS > 1, 99.7 pg/ml; p = 0.044. The prognostic accuracy for prediction of stroke outcome is reflected by an AUC of 0.71 for the 3-month outcome and an AUC of 0.69 for the 12-month outcome (see Figure 1). Conclusion: sNFL levels after ischemic stroke predict clinical outcome after 3 and 12 months.

Objective: Atrial fibrillation (AF) is a major cause for recurrent stroke, has severe impact on a patient's health and imposes a high economic burden for society. Current guidelines recommend 24 h ECG monitoring (standard-of-care, SoC) to detect AF after stroke to reduce the risk of future events. However, paroxysmal AF (PAF) is difficult to detect within this period as it occurs infrequently and unpredictably. In a randomized controlled trial (Find-AF(RANDOMISED)), prolonged and enhanced Holter ECG monitoring (EPM) revealed a significantly higher detection rate of AF compared to SoC, although its cost-effectiveness has not yet been investigated. Methods: Based on the data of FIND-AF(RANDOMISED), an economic evaluation was conducted. One group received EPM for 10 days after the event, and at 3 and 6 months; the other group received SoC. Healthcare resource use and quality of life (QoL) data were measured at baseline, and after 6 and 12 months. Incremental costs and quality-adjusted life years (QALYs) between both groups were compared. Non-parametric bootstrapping and one-way-sensitivity analyses were performed. Results: A total of 281 patients with healthcare resource use and QoL data for all measurement points were considered in the economic evaluation (complete case analysis, CCA). The CCA yielded nonsignificant 315euro lower mean costs and 0.0013 less QALYs for patients receiving EPM with no statistically significant differences in any cost categories. Sensitivity analyses revealed robust results. Bootstrapping the results indicated moderate probability of cost-effectiveness. Conclusions: EPM yielded reduced not significantly different costs without affecting QoL and may be a useful strategy to detect PAF in acute ischemic stroke patients in time.

ObjectiveProlonged monitoring times (72 hours) are recommended to detect paroxysmal atrial fibrillation (pAF) after ischemic stroke but this is not yet clinical practice; therefore, an individual patient selection for prolonged ECG monitoring might increase the diagnostic yield of pAF in a resource-saving manner.MethodsWe used individual patient data from 3 prospective studies (ntotal = 1,556) performing prolonged Holter-ECG monitoring (at least 72 hours) and centralized data evaluation after TIA or stroke in patients with sinus rhythm. Based on the TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guideline, a clinical score was developed on one cohort, internally validated by bootstrapping, and externally validated on 2 other studies.ResultspAF was detected in 77 of 1,556 patients (4.9%) during 72 hours of Holter monitoring. After logistic regression analysis with variable selection, age and the qualifying stroke event (categorized as stroke severity with NIH Stroke Scale [NIHSS] score ≤5 [odds ratio 2.4 vs TIA; 95% confidence interval 0.8–6.9, p = 0.112] or stroke with NIHSS score >5 [odds ratio 7.2 vs TIA; 95% confidence interval 2.4–21.8, p < 0.001]) were found to be predictive for the detection of pAF within 72 hours of Holter monitoring and included in the final score (Age: 0.76 points/year, Stroke Severity NIHSS ≤5 = 9 points, NIHSS >5 = 21 points; to Find AF [AS5F]). The high-risk group defined by AS5F is characterized by a predicted risk between 5.2% and 40.8% for detection of pAF with a number needed to screen of 3 for the highest observed AS5F points within the study population. Regarding the low number of outcomes before generalization of AS5F, the results need replication.ConclusionThe AS5F score can select patients for prolonged ECG monitoring after ischemic stroke to detect pAF.Classification of evidenceThis study provides Class I evidence that the AS5F score accurately identifies patients with ischemic stroke at a higher risk of pAF.

Introduction: Atrial fibrillation remains one of the most common causes of ischemic stroke. The diagnosis of paroxysmal atrial fibrillation (pAF) frequently escapes routine diagnostic due to its intermittent and asymptomatic occurrence. Currently prolonged monitoring times (72h) are recommended, but did not find their way into everyday practice. Therefore an individual patient selection for prolonged ECG-monitoring might increase the diagnostic yield of pAF in a resource-saving and cost-effective manner. Methods: We used individual patient data from three prospective studies (n total =1556) which performed a prolonged Holter ECG-monitoring (at least 72 h) and centralized data evaluation after ischemic stroke (IDEAS 72h monitoring, Find-AF 7 days and Find-AF randomised 3 times 10 days monitoring) in patients presenting with sinus rhythm. The score was developed on the IDEAS cohort and internally (bootstrapping) and externally (Find-AF and Find-AF randomised data) validated following the TRIPOD guideline. Results: pAF was detected in 77 of 1556 patients (49 (4.3%) IDEAS, 20 (9.0%) Find-AF, 8 (4.0%) Find-AF randomized ). After logistic regression analysis with variable selection, age and the qualifying stroke event (categorised as stroke with NIH-SS 5 (OR 7.2; 95% CI 2.4-21.8, pA ge, S troke S everity: NIHSS > 5 , ASS5 ). The score was shown to keep its discriminative performance (IDEAS, AUC 0.76) on the external validation cohort (Find-AF, Find-AF-randomized, AUC 0.75). When ASS5-score and CHADS2-score were applied to classify patients into high and low-risk patients according to the score’s particular Youden-index, the ASS5-score was statistically significant better in discriminating between high- and low-risk patients than the CHADS 2 -score (NRI 0.22 with p=0.047; ROC-AUC 0.75 for ATISS5 and 0.61 for CHADS 2 -Score with p = 0.0032). Conclusion: ASS5-score can be used by clinicians to select patients for prolonged ECG-monitoring after ischemic stroke to detect pAF.

Background: Detecting concealed paroxysmal atrial fibrillation (pAF) is a major focus in the workup of ischemic-stroke-patients. The minimal ECG-monitoring for stroke patients was recently expanded from 24 to 72 hours. However, it has been shown that even more prolonged monitoring reveals further pAF-cases. Our aim was to determine, whether known predictors for underlying pAF differ between stroke patients with AF that occurs on shorter (72h) or more prolonged ECG-monitoring (>72h). Methods: The Find-AF RANDOMISED -trial (NCT01855035) evaluated 3x10-day Holter-ECG vs. standard-care in patients > 60 years with acute ischemic strokes with the primary endpoint of novel pAF after 6 months. In this subanalysis we included only patients in the intervention arm. We compared relevant clinical characteristics (age, gender, body-mass-index = BMI and stroke severity, expressed by the Natrional Institute of Health Stroke Scale, NIHSS-Score), echocardiographic signs of left atrial (LA) dilation (LA diameter, left atrial volume index), blood levels of brain natriuretic peptide (BNP) and rates of supraventricular ectopic activity (longest supraventricular, SV-runs and atrial premature beats, APB) during the AF-free intervals of the first 10-day-Holter-ECG. Results: 402 patients were initially included, 200 in the intervention were analyzed. Baseline characteristics including age (72 65;80 vs. 72 years, 65;76; p = 0.227), gender (55.6 % females vs. 40.5 %; p = 0.149) and NIHSS-Score (4, 2:9 vs. 3, 1;5; p = 0.069) were similar between patients with and without AF. Those with pAF showed significantly larger left atria (LAVI 38.95 ml/m 2 36.13;55.56 vs. 33.3, 26.6;43.5; p = 0.019), longer SV-runs (20, 13;30 vs. 13, 9;20; p = 0.007), more frequent APB/h (19.73, 2.45;47.5 vs. 1.82, 0.53;14.1; p < 0.001) and increased BNP-levels (56 ng/l 30;194 vs. 25, 11;57; p < 0.001). However, we found no significant differences between those with AF detected during standard (72 hour-) and prolonged (>72 hour-) ECG-monitoring. Conclusions: There are no relevant characteristic differences between patients with AF detected during standard 72-hour- and prolonged ECG-monitoring.

Beinahe jeder zweite Patient mit kryptogenem Schlaganfall hat ein persistierendes Foramen ovale (PFO). Das Konsensuspapier stellt zuerst die aktuelle Evidenz des interventionellen PFO-Verschlusses zusammen. Im Weiteren wird das Nutzen-Risiko-Verhaltnis der antithrombozytaren Therapie mit und ohne orale Antikoagulation im Verhaltnis zum PFO-Verschluss abgewogen. Abschliesend werden konsentierte Empfehlungsgrade formuliert. Sowohl der Nutzen der interventionellen als auch das Risiko der medikamentosen Behandlung waren bisher unzureichend belegt. Mit der Veroffentlichung weiterer randomisierter kontrollierter Studien und Metaanalysen lasst sich die Abwagung der Therapieoptionen valide beurteilen. Es zeigt sich eine signifikante Reduktion in der Inzidenz von erneuten Schlaganfallen bei Patienten mit interventionellem PFO-Verschluss im Vergleich zur medikamentosen Therapie. Die Komplikationsrate des interventionellen PFO-Verschlusses ist sehr niedrig. Die vorliegenden Daten zeigen, dass der interventionelle Verschluss des PFO einer alleinigen medikamentosen Therapie bei Patienten mit kryptogenem Schlaganfall im Alter unter 60 Jahren uberlegen ist.

ZusammenfassungDas vorliegende Positionspapier zur Detektion von Vorhofflimmern nach ischämischem Schlaganfall beinhaltet eine Stellungnahme der Arbeitsgemeinschaft „Herz und Hirn“ der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e. V. (DGK) und der Deutschen Schlaganfallgesellschaft e. V. (DSG), die in Zusammenarbeit mit der Stroke Unit-Kommission der DSG und dem Kompetenznetz Vorhofflimmern (AFNET) e. V. erstellt wurde.Vorhofflimmern ist in den Leitlinien der Europäischen Gesellschaft für Kardiologie als eine mindestens 30 Sekunden anhaltende Episode einer Vorhofarrhythmie mit fehlenden P-Wellen definiert. Die 30-Sekundengrenze ist arbiträr gewählt und es ist unbekannt, ob das Schlaganfallrisiko bei Episoden von länger als 30 Sekunden höher ist als bei kürzeren Episoden. Bei Patienten, die einen Schlaganfall erlitten haben, sollte die Detektion von Vorhofflimmern üblicherweise zu einer Umstellung der medikamentösen Sekundärprävention führen, da eine orale Antikoagulation einer Thrombozytenaggregationshemmung überlegen ist. Die Detektion eines bis dato nicht diagnostizierten Vorhofflimmerns sollte daher bei Patienten mit ischämischem Schlaganfall verbessert werden, um die medikamentöse Sekundärprävention des Schlaganfalls zu optimieren. In diesem Positionspapier werden interdisziplinär erarbeitete Standards für eine „strukturierte Rhythmusvisite“ auf der Stroke Unit und ein diagnostisches „Stufenschema“ zur Detektion von Vorhofflimmern vorgeschlagen. Das Positionspapier fasst zudem den gegenwärtigen Kenntnisstand zur Detektion von Vorhofflimmern nach ischämischem Schlaganfall zusammen. Das Positionspapier soll den in der Versorgung von Schlaganfallpatienten tätigen Ärzten eine Handhabe geben, auch wenn bisher nicht abschließend geklärt ist, wie lange und mit welcher EKG-Methode Schlaganfallpatienten ohne bisher bekannte Herzrhythmusstörung bestmöglich monitoriert werden sollten. Dem Charakter eines Positionspapiers angemessen, wurde auf die Kennzeichnung von Evidenzgraden verzichtet, da es sich überwiegend um die Meinung von Experten handelt, die auf berichteten Fallserien und klinischer Erfahrung beruht und somit nicht mit einer Leitlinie gleichzusetzen ist und so auch nicht verstanden werden will.

This expert opinion paper on atrial fibrillation detection after ischemic stroke includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. This paper was endorsed by the Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork. In patients with ischemic stroke, detection of atrial fibrillation should usually lead to a change in secondary stroke prevention, since oral anticoagulation is superior to antiplatelet drugs. The detection of previously undiagnosed atrial fibrillation can be improved in patients with ischemic stroke to optimize stroke prevention. This paper summarizes the present knowledge on atrial fibrillation detection after ischemic stroke. We propose an interdisciplinary standard for a "structured analysis of ECG monitoring" on the stroke unit as well as a staged diagnostic scheme for the detection of atrial fibrillation. Since the optimal duration and mode of ECG monitoring has not yet been finally established, this paper is intended to give advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on the expert opinion, reported case series and clinical experience. Therefore, this paper is not intended as a guideline.

Die Definition, wann ein ischamischer Schlaganfall als „kryptogen“ bezeichnet wird, wird in der aktuellen Literatur uneinheitlich gefuhrt. Insbesondere die kardiologische Diagnostik, die hier zur Abklarung des Schlaganfalls obligatorisch durchgefuhrt werden sollte, variiert stark. Daher ist es nicht verwunderlich, dass der Anteil von kryptogenen Schlaganfallen in den publizierten Studien einer grosen Schwankungsbreite unterliegt. Gerade in dieser Gruppe wird aber vermutet, dass haufig ein unentdecktes, paroxysmales Vorhofflimmern (VHF) fur den Schlaganfall verantwortlich gewesen sein konnte. Gehen aktuelle Empfehlungen davon aus, dass bei V. a. einen kardioembolischen Schlaganfall ein 24 h-Holter-EKG durchgefuhrt werden sollte, so zeigen inzwischen uberzeugende Daten, dass ein prolongiertes EKG-Monitoring signifikant haufiger VHF zu detektieren vermag. Dies hatte in den meisten Fallen fur den Patienten direkte therapeutische Konsequenzen, da dann eine orale Antikoagulation indiziert ware, wodurch effektiv die Re-Schlaganfallrate gesenkt werden konnte. In der vorliegenden Arbeit werden die aktuellen Studien zur Detektion von VHF nach einem stattgehabten ischamischen Schlaganfall referiert, typische offene Fragestellungen diskutiert und die Entwicklung hinsichtlich Therapie und Langzeit-EKG-Diagnostik erortert.

BACKGROUND AND PURPOSE: Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. METHODS: Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). RESULTS: Predicted lifelong discounted costs were 33,837 for patients diagnosed by the 7-d-Holter and 33,852 by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 /QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. CONCLUSIONS: A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness. peerReviewed

International journal of stroke 12(4), 412-415 (2017). doi:10.1177/1747493016677986, Published by Sage, London

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.

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. peerReviewed

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. peerReviewed

PurposeCarotid 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.MethodsThis 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.ResultsNew 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.ConclusionsThe 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.

The contribution of the ipsilateral (nonaffected) hemisphere to recovery of motor function after stroke is controversial. Under the assumption that functionally relevant areas within the ipsilateral motor system should be tightly coupled to the demand we used fMRI and acoustically paced movements of the right index finger at six different frequencies to define the role of these regions for recovery after stroke. Eight well‐recovered patients with a chronic striatocapsular infarction of the left hemisphere were compared with eight age‐matched participants. As expected the hemodynamic response increased linearly with the frequency of the finger movements at the level of the left supplementary motor cortex (SMA) and the left primary sensorimotor cortex (SMC) in both groups. In contrast, a linear increase of the hemodynamic response with higher tapping frequencies in the right premotor cortex (PMC) and the right SMC was only seen in the patient group. These results support the model of an enhanced bihemispheric recruitment of preexisting motor representations in patients after subcortical stroke. Since all patients had excellent motor recovery contralesional SMC activation appears to be efficient and resembles the widespread, bilateral activation observed in healthy participants performing complex movements, instead of reflecting maladaptive plasticity. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.

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 ≥ 70 years = 1 point, age ≥ 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 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.

Background and Purpose— Against the background of a relatively low rate of clinical events during carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA), diffusion-weighted imaging (DWI) is increasingly being used to compare the incidence of new ischemic lesions after both procedures. In addition, DWI may also provide a means of defining the role of different CAS techniques on this adverse outcome. Therefore, we performed a PubMed search and systematically analyzed all peer-reviewed studies published between January 1990 and June 2007 reporting on the occurrence of new DWI lesions after CAS or CEA. Summary of Review— In 32 studies comprising 1363 CAS and 754 CEA procedures, the incidence of any new DWI lesion was significantly higher after CAS (37%) than after CEA (10%) ( P P P P P Conclusions— New DWI lesions occur more frequently after CAS than after CEA. However, technical advances mainly in the field of endovascular therapy potentially reduce the incidence of these adverse ischemic events. In this scenario, DWI appears to be an ideal tool to compare and further improve both techniques.

Background and purpose: Aortic arch calcification (AC) on conventional angiograms has recently been shown to be associated with embolic complications during carotid artery stenting (CAS). Because conventional angiography is not routinely carried out in patients prior to CAS, a less invasive, commonly available diagnostic modality is warranted to identify AC. Methods: We investigated the occurrence of AC on routinely acquired chest radiographs and its influence on diffusion-weighted imaging (DWI) lesions as surrogate markers for stroke. Results: A total of 152 patients (mean age: 67.5 ± 8.9 years, 112 men) underwent CAS and completed pre- and post-procedural DWI. AC larger than 1 cm in length was classified as relevant and could be detected in 63 patients (41.4%) on plain chest radiographs. In patients with AC, significantly more new DWI-lesions were found than in patients without AC [median 2; interquartile range (IQR): 0–7 vs. median 1, IQR: 0–2; P

Background and Purpose— Prospective data on the safety of endovascular thrombectomy in acute stroke patients on non–vitamin K antagonist oral anticoagulants are lacking. Methods— Prospective multicenter observational study. Patients with ischemic stroke undergoing thrombectomy with or without preceding thrombolysis were enrolled into the Registry of Acute Ischemic Stroke Under New Oral Anticoagulants. Baseline characteristics and functional outcome at 3 months were assessed. Hemorrhagic transformation and symptomatic intracranial hemorrhage were analyzed. Reperfusion was graded using the modified Thrombolysis in Cerebral Infarction score. Results— Of 28 patients treated with thrombectomy, 5 had received also systemic thrombolysis (18%). Intracranial hemorrhage was observed in 46%, but symptomatic intracranial hemorrhage occurred only in 1 patient. Successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b–3) was achieved in 59%. At 3 months, 19% had a modified Rankin Scale score of 0 to 2, and mortality was 26%. Conclusions— Thrombectomy in non–vitamin K antagonist oral anticoagulant patients seems safe although a comparatively high rate of asymptomatic hemorrhagic transformation was noted. Confirmation in larger prospective controlled cohorts is necessary. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01850797.

Atherosclerotic disease of the carotid arteries is responsible for a significant portion of ischemic strokes. Carotid endarterectomy (CEA) is currently the accepted standard of treatment for patients with severe symptomatic carotid stenosis. In the past few years, however, carotid angioplasty and stenting (CAS) has emerged as a potential alternative endovascular treatment strategy for this disorder. In fact, spurred by the positive results of single center studies and small, pivotal randomized trials, some even consider CAS as the treatment modality of choice, especially in presumably surgical high-risk patients. Yet, randomized trials directly comparing CAS with CEA are sparse and have produced conflicting results. The aim of this article is to review the current trial data on this issue and to define the role of these techniques for the management of two important subgroups of patients. An updated meta-analysis of seven randomized trials comparing CEA with CAS demonstrates that CAS is associated with a significantly increased risk of any stroke or death within 30 days (OR. 1.41, 95% CI 1.07-1.87, p < 0.05). Focusing on patients with a symptomatic carotid stenosis, there was also a significant difference in the odds of treatment-related stroke and death between CAS and CEA (OR, 1.41 ; CI 1.05 to 1.88, p < 0.05). Data on all disabling strokes and deaths within 30 days was available from five trials. The odds of disabling stroke or death at 30 days were similar in the endovascular and surgical group (OR, 1.33, 95% CI 0.89 to 1.98). Overall, these data do not justify a blind enthusiasm for CAS and a widespread use of this procedure for the treatment of carotid artery stenosis. On the other hand, a closer inspection of the current literature on elderly patients and those with a contralateral carotid occlusion clearly indicates that CAS and CEA already now have a complementary role. While elderly patients should preferentially be treated with CEA, CAS appears to be the treatment of choice in patients with a symptomatic carotid artery stenosis and a contralateral carotid occlusion in experienced centers.

Background and Purpose— Diffusion-weighted imaging (DWI) may be a useful tool to evaluate the efficacy of cerebral protection devices in preventing thromboembolic complications during carotid angioplasty and stenting (CAS). The goals of this study were (1) to compare the frequency, number, and size of new DWI lesions after unprotected and protected CAS; and (2) to determine the clinical significance of these lesions. Methods— DWI was performed immediately before and within 48 hours after unprotected or protected CAS. Clinical outcome measures were stroke and death within 30 days. Results— The proportion of patients with any new ipsilateral DWI lesion (49% versus 67%; P P P Conclusions— The use of cerebral protection devices significantly reduces the incidence of new DWI lesions after CAS of which the majority are asymptomatic and less than 10 mm in diameter. The frequent occurrence of these lesions and their close correlation with the clinical outcome indicates that DWI could become a sensitive surrogate end point in future randomized trials of unprotected versus protected CAS.

To the Editor: We read with great interest the article of Ritter et al,1 which nicely demonstrates that the prolongation of ECG monitoring time increases the detection rate of paroxysmal atrial fibrillation in stroke patients, a result that is in concordance with existing literature. One aspect especially drawn to our attention was the lower yield of the Holter monitoring during simultaneous ECG recording as compared with the implantable loop recorder (ILR). ILRs only store automatically triggered episodes and can detect only atrial fibrillation (AF) episodes of ≥2 minutes, whereas Holter ECGs store (usually semiautomatically analyzed) continuous recordings and …

Diagnosis of paroxysmal atrial fibrillation (AF) in stroke patients is challenging, but highly clinically relevant. The percentage of stroke patients with permanent AF increases with age, but limited data are available for the age-dependent yield of paroxysmal AF by Holter monitoring. Patients with acute cerebral ischemia were included into the prospective observational Find-AF study. Patients free from AF at presentation received 7 day Holter monitoring. We calculated the percentage of otherwise undetected paroxysmal AF and the number needed to screen for age groups under 60 years, and in 5 year clusters from the age of 60 up to 85 and older. 272 patients were included, 43 (15.8 %) had AF at admission, 33 patients with paroxysmal AF were identified by 7 day Holter (n = 29) or medical history (n = 4).The yield of 7 day Holter ECG clearly increased with older age (p = 0.004)

Background and purpose Detection of paroxysmal atrial fibrillation (pAF) after an ischaemic cerebrovascular event is of imminent interest, because oral anticoagulation as a highly effective secondary preventive treatment is available. Whereas permanent atrial fibrillation (AF) can be detected during routine electrocardiogram (ECG), longer detection duration will detect more pAF but might be resource consuming. The current study tried to identify clinical predictors for pAF detected during long-term Holter ECG and clinical follow-up. Methods Patients with acute ischaemic stroke were prospectively investigated with an intensified algorithm to detect pAF (7-day Holter ECG, follow-up investigations after 90 days and 1 year). Results Two hundred and eighty-one patients were included, 44 of whom had to be excluded since they presented with permanent AF and another 13 patients had to be excluded due to other causes leaving 224 patients (mean age 68.5 years, 58.5% male). Twenty-nine (12.9%) patients could be identified to have pAF during prolonged Holter monitoring, an additional 13 (5.8%) after follow-up investigations. Multivariate analysis identified advanced age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01–1.08] as well as clinical symptoms >24 h (OR 5.17, 95% CI 1.73–15.48) and a history of coronary artery disease (OR 3.14, 95% CI 1.35–7.28) to be predictive for the detection of pAF. Conclusions In acute stroke patients with advanced age, history of coronary artery disease and clinical symptoms >24 h, a prolonged Holter ECG monitoring and follow-up is warranted to identify pAF. This could increase the detection rate of patients requiring anticoagulation and may be able to reduce the risk of recurrent stroke in the case of successful anticoagulation of these patients.

More than three decades ago, an analysis from the Framingham Heart Study revealed that atrial fibrillation (AF) increases the risk of stroke by a factor of five in non-rheumatic AF and by a factor of 17 in rheumatic AF.1 Since then, it has convincingly been shown that anticoagulation is one of the most effective secondary stroke prophylactic treatment options, which reduces the risk of stroke by 2/3,2 even in an older population.3 AF may occur in different types and in an individual patient often starts with paroxysmal AF, but later becomes persistent or permanent AF.4 Interestingly, the risk of stroke or systemic embolism is influenced by cardiovascular risk factors such as hypertension, diabetes or history of stroke, but not by type of AF.5 Most patients with paroxysmal AF had never reported typical clinical symptoms, which supports the argument of a clinically silent disease, especially during the earlier stages.6 Within the last few years, research interest has grown in the clinical relevance of AF at an even earlier stage, before the clinical detection of AF. It has now convincingly been shown that the first manifestation of clinical AF is often preceded by short episodes of ‘subclinical’ or ‘undiagnosed' AF. These data are mostly derived from patients with implantable pacemaker devices which allow a continuous monitoring of cardiac rhythm and are often able to record changes in it.7 ,8 Earlier this year, the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) investigators reported data on 2580 hypertensive older pacemaker patients.9 These patients were aged 65 years or older and had recently been implanted with a pacemaker or defibrillator. Patients with a history of AF or atrial flutter and patients on oral anticoagulation with a …

Background Patients with a cerebral ischemic event are at high risk of recurrent ischemia and other cardiovascular events. Clinical scores are recommended to predict cardiovascular risk in patients with cerebral ischemia to inform secondary preventive measures. Biomarkers may improve risk prediction beyond clinical scores and therefore secondary prevention. Methods Within the observational Find-AF trial (ISRCTN 46104198), 197 patients aged >18 years with cerebral ischemia and without atrial fibrillation had blood sampled at baseline and completed 1-year follow-up. Predictive value of 5 novel cardiovascular biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2), National Institutes of Health Stroke Scale (NIH-SS) and Modified Rankin Scale (MRS). Results There were 23 vascular events (11.7%) and 13 deaths (6.6%) during 1 year. In multivariate analyses of all 5 markers, only high-sensitivity Troponin T (hs-TropT) remained significantly predictive of vascular events (p=0.045) and all-cause mortality (p=0.004). Hs-TropT was higher in patients with a vascular event (median 12.7 [6.8; 49.6] ng/mL vs. 5.1 [1.5; 11.7] ng/mL) and patients with hs-TropT above the median of 6.15 ng/mL were more likely to have a vascular event (Hazard Ratio 4.0, p=0.006 on log-rank test). For prediction of vascular events as well as all-cause mortality, hs-TropT significantly contributed to multivariate Cox-regression models with ESRS, SPI-2, or each combined with NIH-SS or MRS as covariates. C-statistic increased numerically from 0.689 (ESRS) to 0.743 (ESRS+hs-TropT) and 0.696 (SPI-2) to 0.758 (SPI-2+hs-TropT) (p=n.s.). Areas under the receiver-operator characteristics curves for vascular events were 0.694 (SPI-2), 0.712 (ESRS), 0.743 (ESRS+hs-TropT), 0.755 (hs-TropT) and 0.760 (SPI-2+hs-TropT). No patient with a low-risk ESRS ≤2 and a hs-TropT below the median had a vascular event during 1 year follow-up. Conclusion Hs-TropT is predictive of major vascular events and all-cause mortality in patients with cerebral ischemia and improves prediction by established clinical scores.

Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (

Background and Purpose— We assessed whether echocardiography can predict paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia presenting in sinus rhythm. Methods— Within the prospective Find-AF cohort, 193 consecutive patients with cerebral ischemia and sinus rhythm on presentation had evaluation of echocardiographic parameters of left atrial size and function. PAF was diagnosed by 7-day Holter monitoring. Results— In 26 patients with PAF, late diastolic Doppler (A) and tissue Doppler (a′) velocities were lower whereas left atrial diameter, left atrial volume index (LAVI), LAVI/A, and LAVI/a′ were larger ( P Conclusions— LAVI/a′

Background and Purpose— Diagnosis of paroxysmal atrial fibrillation is difficult but highly relevant in patients presenting with cerebral ischemia yet free from atrial fibrillation on admission. Early initiation and prolongation of continuous Holter monitoring may improve diagnostic yield compared with the standard of care including a 24-hour Holter recording. Methods— In the observational Find-AF trial (ISRCTN 46104198), consecutive patients presenting with symptoms of cerebral ischemia were included. Patients free from atrial fibrillation at presentation received 7-day Holter monitoring. Results— Two hundred eighty-one patients were prospectively included. Forty-four (15.7%) had atrial fibrillation documented by routine electrocardiogram on admission. All remaining patients received Holter monitors at a median of 5.5 hours after presentation. In those 224 patients who received Holter monitors but had no previously known paroxysmal atrial fibrillation, the detection rate with early and prolonged (7 days) Holter monitoring (12.5%) was significantly higher than for any 24-hour (mean of 7 intervals: 4.8%, P =0.015) or any 48-hour monitoring interval (mean of 6 intervals: 6.4%, P =0.023). Of those 28 patients with new atrial fibrillation on Holter monitoring, 15 (6.7%) had been discharged without therapeutic anticoagulation after routine clinical care (ie, with data from 24-hour Holter monitoring only). Detection rates were 43.8% or 6.3% for short supraventricular runs of ≥10 beats or prolonged episodes (>5 hours) of atrial fibrillation, respectively. Diagnostic yield appeared to be only slightly and not significantly increased during the first 3 days after the index event. Conclusions— Prolongation of Holter monitoring in patients with symptoms of cerebral ischemic events increases the rate of detection of paroxysmal atrial fibrillation up to Day 7, leading to a relevant change in therapy in a substantial number of patients. Early initiation of monitoring does not appear to be crucial. Hence, prolonged Holter monitoring (≥7 days) should be considered for all patients with unexplained cerebral ischemia.