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Zusammenfassung Hintergrund Kontinuierliche periphere Nervenblockaden (Continuous peripheral nerve blocks, CPNB) werden am häufigsten zur perioperativen Analgesie bei chirurgischen Eingriffen eingesetzt. Alternative Indikationen wie die Behandlung tumorbedingter Schmerzen sind die Ausnahme, gleichwohl das Verfahren auch hier effektiv eingesetzt werden kann. Fallbericht Bei einer 59-jährigen Patientin mit Bronchialkarzinom konnte der durch Metastasierung in der Tibia verursachte starke Schmerz mittels 28-tägiger CPNB des N. ischiadicus und des N. saphenus bis zu ihrem Versterben effektiv behandelt werden. Neben der Schmerzreduktion auf ein Minimum wurde die vorhergehende opioidassoziierte Vigilanzminderung verringert, wodurch sich die Lebensqualität in der letzten Lebensphase steigern ließ. Schlussfolgerungen CPNB können auch in der Palliativmedizin regional begrenzte Schmerzen effektiv behandeln. Aufgrund der notwendigen Versorgungsstrukturen wird es aber ein Verfahren bleiben, das nur für einzelne Palliativpatient*innen sinnvoll und indiziert ist.

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.

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.

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 (

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: The cardiac diagnostic workup of stroke patients, especially the value of echocardiography and prolonged and enhanced Holter-ECG monitoring (EPM), 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-AF RANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to EPM or usual stroke unit care. Therapeutic consequences of echocardiography and routine Holter-ECG or EPM, respectively, were compared and one-year mortality was calculated. Results: 50.3% received EPM and 49.7% routine ECG monitoring. 82.9 % underwent transthoracic echocardiography (TTE), 38.9 % transesophageal echocardiography (TEE) and 25.6 % both procedures. 14/90 TEE pathologies and 1/89 TTE pathology led to a change in therapy, resulting in a number needed to change decision (NNCD) of 12 and 334, respectively. In comparison, EPM 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). We found a trend towards a higher one-year mortality in patients with pathologic echocardiographic findings (p = 0.093). Conclusions: Most changes in therapeutic decisions were caused by EPM, 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.

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.

Catheter ablation of atrial fibrillation (AF) improves left ventricular (LV) function in patients with LV systolic dysfunction, suggestive of underlying arrhythmia-induced adverse remodeling.The objectives of this study were to evaluate whether arrhythmia-induced LV remodeling occurs in patients with AF and preserved LV systolic function and to assess whether this remodeling is reversible after restoration of sinus rhythm by catheter ablation.Forty-three patients with AF and preserved LV systolic function (LV ejection fraction 62% ± 7%) underwent cardiovascular magnetic resonance (CMR) imaging before catheter ablation including native T1 mapping using a modified Look-Locker inversion recovery sequence. Twenty-five patients underwent follow-up CMR 3 months after catheter ablation. Twenty-two matched controls without AF underwent the same CMR protocol.Patients with AF had higher baseline LV native T1 values than did controls (1296 ± 55 ms vs 1243 ± 55 ms; P.01). During a median follow-up of 9 months (interquartile range 4-14 months), 17 patients (40%) experienced AF recurrence. No differences in baseline T1 values were observed between patients with and without AF recurrence. There was a significant decrease in native T1 values in patients with successful restoration of sinus rhythm after catheter ablation at 3 months of follow-up CMR (1300 ± 45 ms vs 1270 ± 55 ms; P.01), while they remain unchanged in patients with AF recurrence (1303 ± 51 ms vs 1309 ± 31 ms; P = .64).These preliminary results suggest that subclinical arrhythmia-induced LV structural remodeling occurs in patients with AF and preserved LV systolic function. This remodeling might be reversible after catheter ablation with successful restoration of sinus rhythm as quantified noninvasively and gadolinium-free by CMR native T1 mapping.

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.

Hintergrund und Fragestellung | Die Rolle von Biomarkern bei asymptomatischer diastolischer Dysfunktion (DD) ist bislang wenig untersucht. Die vorliegende Arbeit untersuchte daher die klinischen Assoziationen und diagnostischen Fahigkeiten verschiedener Biomarker bei asymptomatischer DD. Methodik | 188 gesunde Probanden (linksventrikulare Ejektionsfraktion ≥ 50 %, 50–85 Jahre) ohne kardiovaskulare Risikofaktoren wurden prospektiv im Rahmen einer bevolkerungsbasierten Beobachtungsstudie rekrutiert. Von diesen hatten n = 103 eine echokardiografisch definierte DD (Grad ≥ 1), n = 85 Patienten ohne DD wurden dem Kontrollkollektiv (KON) zugeordnet. wurden standardisiert durchgefuhrt. Ergebnisse | GDF-15, MRproADM und CTproAVP waren in der DD-Gruppe im Vergleich zur Kontrollgruppe signifikant erhoht: Es zeigte sich fur GDF-15, MRproADM und CTproAVP eine signifikante Assoziation zum Vorliegen einer DD (Grad ≥ 1). Diese Assoziationen waren jedoch nach multipler Adjustierung nicht mehr nachweisbar. Zum linksventrikularen Fullungsindex (E / e’) als kontinuierlichen Parameter der diastolischen Funktion zeigten NTproBNP, MRproANP, MRproADM, nicht aber GDF-15, CTproET1 und CTproAVP signifikante bivariate Korrelationen. Diese Assoziationen waren nach multipler Adjustierung nicht mehr nachweisbar. Keiner der untersuchten Biomarker zeigte in den ROC-Analysen eine ausreichende Diskriminationsfahigkeit zur Unterscheidung zwischen DD und gesunden Probanden. Folgerungen | Im Gegensatz zu NTproBNP, MRproANP und CTproET1 waren die Plasmakonzentrationen von GDF-15, MRproADM und CT-proAVP bei Probanden mit einer DD im Vergleich zur Kontrollgruppe signifikant erhoht. Nach Adjustierung fur Alter, Geschlecht, BMI und GFR war der Zusammenhang der Biomarker zur DD und zu E / e’ nicht mehr nachweisbar. Keiner der untersuchten Biomarker zeigte eine ausreichende diskriminatorische Fahigkeit zur Detektion einer DD.

Background: Three randomised controlled trials have investigated prolonged monitoring methods for the detection of Atrial Fibrillation (AF) in stroke patients. All have shown that more patients with Atrial Fibrillation are detected by prolonged monitoring, but none has so far investigated if biomarkers identify patients who benefit from the intervention. BNP is of special interest, has retrospective analyses from the WARSS trial showed that BNP identifies patients who might benefit from oral anticoagulation in comparison to Aspirin (Longstreth, Stroke 2013). Methods: We analysed brain natriuretic peptide (BNP) measured at randomisation in participants of the Find-AF randomised trial. In brief, Find-AF randomised randomised 402 stroke patients aged 60 years and above with a recent stroke (< 7 days to onset of symptoms) to enhanced and prolonged monitoring (3x10 day Holter ECG) or usual care. The primary endpoint was the detection of AF by 6 months. Results: BNP could be measured in 373 of 402 participants (93 %). Patients with AF detected by 6 months had significantly higher BNP values (median 53; IQR 30;169) as compared to patients without AF (median 28; IQR 12;62) (p= 100 pg/ml versus < 100 pg/ml showed a significant interaction with the intervention (p=0.01). The number needed to screen in the overall study was 11, while it was 3 for BNP>100pg/ml and 18 for BNP Conclusion: BNP identifies a high-risk subgroup of stroke patients with undetected AF.

Introduction: The intensity of AF detection modalities in stroke patients has been modulated by the stroke subtype. Hence, most studies have been performed in so called cryptogenic stroke. However, it has never been proven that AF is more prevalent in cryptogenic stroke as compared to non-cryptogenic stroke. The Find-AF randomised trial (ISRCTN 46104198) is a randomised trial comparing prolonged Holter ECG monitoring (3x 10 day monitoring) and usual care in 400 patients with ischemic stroke. The primary results of Find-AF randomised will be submitted for presentation as a late breaking clinical trial to ISC 2016. In contrast to previous randomised trials (e. g. EMBRACE and CRYSTAL-AF), this trial will include all ischemic stroke patients, not only cryptogenic strokes. Hypothesis: We hypothesized that the AF detection rate is independent from the stroke subtype according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST), but is associated with clinical variables (e. g. age, NIHSS, prevalence of coronary artery disease). Methods: 402 patients with ischemic stroke were recruited on certified stroke units within seven days after the index event. Stroke was classified by the Trial of Org 10172 in Acute Stroke Treatment (TOAST), dividing the patient collective into five subgroups according to the most likely stroke etiology. Results: The following table presents a preliminary assessment of relevant baseline characteristics of 392 participants (full data set will be available upon abstract presentation. In addition, all index strokes will be independently assessed by an adjudication committee, consisting of three neurologists. We will present AF detection rates in different stroke subtypes. Conclusion: If our hypothesis is correct, future studies on AF detection in stroke patients should not be confined to stroke subtypes (e. g. cryptogenic or embolic stroke of unknown source), but rather include clinical parameters to increase the probability of finding AF.

Introduction: Undiagnosed atrial fibrillation (UAF) is a major burden in ischemic stroke. However, randomised trials have partly shown astonishingly low AF detection rates (e. g. in the CRYSTAL-AF study). This may be due to differences in baseline and stroke characteristics between studies. Hypothesis: We hypothesized that stroke patients in a randomised controlled trial have less severe strokes than patients in an observational trial with similar inclusion and exclusion criteria. Methods: We used data from the Find-AF observational (NCT 01855035) and the Find-AF randomised controlled trial (ISRCTN 46104198). We included only patients at study site Goettingen of the Find-AF randomised controlled trial (n=153) and only included patients from the Find-AF observational trial that fulfilled the inclusion/exclusion criteria of Find-AF randomised (n=90). We compared baseline characteristics of screened versus included patients in Find-AF randomised and baseline characteristics and stroke severity parameters between both studies. Data are shown as mean (Standard Deviation) or Median (25%; 75% percentile) and were compared by chi-square, t-test or Mann-Whitney U test. Results: Table 1 shows as comparison between baseline characteristics of both studies Comparing patients fulfilling the inclusion/exclusion criteria of Find-AF randomised, but unwilling to give informed consent to randomised patients showed a significant difference in age (77 ± 11 vs. 74 ± 8; p< 0.001), but no difference in gender (p=0.581). Conclusions: Both studies included patients similar in age, gender and many comorbidities. Major differences occurred in NIHSS and MRS. As NIHSS is a predictor of atrial fibrillation, randomized controlled trials investigating AF detection should include a minimum NIHSS to avoid a selection bias towards less severe strokes.

The role of biomarkers in asymptomatic diastolic dysfunction (DD) has not been investigated so far. The aim of the study was to evaluate the clinical associations and the diagnostic property of different biomarkers in patients with asymptomatic DD.Within a population based observational study, healthy participants (50-85 years) with an LVEF ≥ 50 % and no cardiovascular risk factor were prospectively identified. Patients were classified as having either DD (grade ≥ 1, n = 103) or no DD (CON: n = 85). All patients underwent physical examination including medical history, six-minute-walk-testing, QoL (SF-36), comprehensive echocardiography and blood sampling to measure routine values and specified biomarkers (NTproBNP, MRproANP, GDF-15, MRproADM, CTproET1, CTproAVP).In the DD-group plasma concentration of GDF-15 (p = 0,002), MRproADM (p 0,001), and CTproAVP (p = 0,003) were significantly higher than in the CON-group. In contrast, NTproBNP (p = 0,390), MRproANP (p = 287), and CTproET1 (p = 0,393) did not differ. GDF-15, MRproADM and CTproAVP were significantly associated with the presence of DD. However, the significance of the seen associations was lost after multiple adjustments. NTproBNP, MRproANP, and MRproADM were significantly related to E / e' as a continuous measure of diastolic function. The significance of the seen associations was lost after multiple adjustments. In ROC analyses, none of the investigated biomarkers was able to relevantly improve the diagnosis of DD.In patients with asymptomatic DD plasma concentrations of GDF-15, MRproADM and CT-proAVP were significantly higher when compared with controls. In contrast, NTproBNP, MRproANP and CTproET1 did not differ. After adjustment for age, sex, BMI and renal function, no significant association between DD or E / e' and different biomarkers could be observed. Furthermore, none of the investigated biomarkers was able to substantially improve the diagnosis of DD.

Background and purpose Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study. Methods Natriuretic peptide levels were analysed in two independent patient cohorts (162 patients with arterial hypertension or other cardiovascular risk factors and 82 patients with retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and BNP were measured before the start of a 7-day Holter monitoring period carefully screened for AT/AF. Results 244 patients were included; 16 had paroxysmal AT/AF. After excluding patients with a history of AT/AF (n=5), 14 patients had newly diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4; 178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9 (201.4; 277.1) versus 90.8 (42.3–141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0; 58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to 0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively. Conclusions NT-proBNP and BNP levels are elevated in patients with silent AT/AF as compared with sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic peptide level initiated Holter monitoring may be a useful strategy in prevention of stroke or systemic embolism.

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 …

Introduction: Detection of paroxysmal atrial fibrillation (PAF) after an ischemic 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. Methods: Patients with acute ischemic stroke were prospectively investigated with an intensified algorithm to detect PAF (7 day Holter ECG, follow-up investigations after 90 days and one year, ISRCTN 46104198). Results: 281 patients were prospectively included in the study, 44 of which had to be excluded since they presented with permanent AF as diagnosed by ECG during admission and another 13 patients due other causes leaving 224 patients (mean age: 68.5 years, 58.5% male) as the final study population. 29 (12.9%) patients could be identified to have PAF during prolonged (median: 6.7 days IQR: 4.4-7.0) Holter monitoring, an additional 8 (3.6%) and 5 (2.2%) patients after follow-up investigations after 90 days and 1 year, respectively. In 182 patients no AF could be detected. Multivariate analysis identified advanced age (Odds ratio (OR) 1.04, 95% confidence interval (CI): 1.01-1.08), a higher initial NIH-SS (OR 1.10, 95% CI: 1.00-1.21) as well as clinical symptoms >24h (OR 3.45, 95% CI: 1.06-11.19) and a history of coronary artery disease (OR 2.74, 95% CI: 1.16-6.50) to be predictive for the detection of PAF. Receiver operation characteristics demonstrated an area under the curve of 0.783 for this model. Neither the results of blood analysis, duplex sonography, cerebral imaging nor routine echocardiography could be found to be independently associated with the detection of PAF. Conclusion: In acute stroke patients with advanced age, history of coronary artery disease, higher NIH-SS scores and ischemic stroke as the presenting event, a prolonged Holter ECG monitoring and follow-up is warranted to identify PAF. This could increase the detection rate of patients requiring anticoagulation and would be expected to reduce the risk of recurrent stroke in case of consequent anticoagulation of these patients.

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.

Background Detection of paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia is challenging. Echocardiography (LAVI/á, an index of left atrial remodeling) can select a subgroup of patients for extended ECG-monitoring. Excessive supraventricular ectopic activity (ESVEA), measured as atrial premature beats (APB) and longest supraventricular run on 24h-Holter-ECG (SV-run 24h ) may further improve prediction of PAF. Methods Retrospective analysis from a prospective monocentric observational trial (Find-AF) in patients >18y with cerebral ischemia (ISRCTN 46104198). PAF was diagnosed by 7d-Holter monitoring. Transthoracic echocardiography parameters were prospectively assessed. ESVEA was quantified in one 24h interval, which had to be free from PAF. For the present analysis, 44 patients with atrial fibrillation at baseline and 20 patients with limited evaluability for ESVEA (9 with pacemaker rhythms, 4 with low-quality recordings and 7 with PAF who had no 24h interval free from PAF) were excluded. Results PAF was detected in 21 out of 215 patients (9.8%) of the analysis population. PAF was more prevalent in those with ESVEA above the median: 17.3 vs. 2.7% for APB > vs. 24h > vs. 24h 10 [7; 18] vs. 0 [0; 8] beats (both p24h ) (p=0.022) were independently predictive for the presence of PAF. 0% of patients with normal LAVI/á and APB 4/h, and 27.1% of those with both abnormal LAVI/á and APB >4/h had PAF (p Conclusions In patients with cerebral ischemia, ESVEA discriminates PAF from Non-PAF beyond clinical factors and LAVI/á. PAF is ruled out in patients with normal LAVI/á and APB 4/h.

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.

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.

Background Detecting paroxysmal atrial fibrillation (AF) in patients with ischemic strokes presenting in sinus rhythm is challenging because episodes are often short, occur randomly, and are frequently asymptomatic. If AF is detected, recurrent thromboembolism can be prevented efficiently by oral anticoagulation. Numerous uncontrolled studies using various electrocardiogram (ECG) devices have established that prolonged ECG monitoring increases the yield of AF detection, but most established procedures are time-consuming and costly. The few randomized trials are mostly limited to cryptogenic strokes. The optimal method, duration, and patient selection remain unclear. Repeated prolonged continuous Holter ECG monitoring to detect paroxysmal AF within an unspecific stroke population may prove to be a widely applicable, effective secondary prevention strategy. Study Design Find-AFRANDOMISED is a randomized and controlled prospective multicenter trial. Four hundred patients 60 years or older with manifest (symptoms ≥24 hours or acute computed tomography/magnetic resonance imaging lesion) and acute (symptoms ≤7 days) ischemic strokes will be included at 4 certified stroke centers in Germany. Those with previously diagnosed AF/flutter, indications/contraindications for oral anticoagulation, or obvious causative blood vessel pathologies will be excluded. Patients will be randomized 1:1 to either enhanced and prolonged Holter ECG monitoring (10 days at baseline and after 3 and 6 months) or standard of care (≥24-hour continuous ECG monitoring, according to current stroke guidelines). All patients will be followed up for at least 12 months. Outcomes The primary end point is newly detected AF (≥30 seconds) after 6 months, confirmed by an independent adjudication committee. We plan to complete recruitment in autumn 2014. First results can be expected by spring 2016.

Blood biomarkers may improve the performance in predicting early stroke outcome beyond well-established clinical factors. We investigated the value of growth-differentiation factor-15 (GDF-15) to predict functional outcome after 90 days in a prospectively collected patient cohort with symptoms of acute ischemic stroke. Two hundred eighty-one patients with symptoms of acute ischemic stroke were prospectively investigated. Serial blood samples for GDF-15 analysis were obtained after the admission of the patient, after 6 and 24 h. Primary outcome was the dichotomized modified ranking scale (MRS) 90 days after the initial clinical event. Within the final study population (264 patients, mean age 70.3 ± 12.7 years, 55.3% male), National Institutes of Health Stroke Scale (NIH-SS) [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.141–1.412, p