Karl Georg Haeusler

Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS)

Atrial fibrillation (AF) confers a substantial risk of mortality and morbidity from stroke and thrombo-embolism, and this common cardiac arrhythmia represents a major healthcare burden in Europe.1 Stroke prevention is central to the management of AF patients, with the 2012 focused update of the European Society of Cardiology (ESC) guidelines2 recommending oral anticoagulation (OAC) using well-controlled adjusted dose vitamin K antagonists (VKAs, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, previously referred to as new or novel OACs3) for patients with AF and ≥1 stroke risk factor(s). Also, these guidelines strongly advocate a clinical practice shift so that the initial decision step now is the identification of ‘truly low risk’ patients, essentially those aged <65 years without any stroke risk factor (both male and female), who do not need any antithrombotic therapy.2 The ESC guidelines also recommend the use of the CHA2DS2-VASc score4 for stroke risk assessment, and define ‘low-risk’ patients as those with a CHA2DS2-VASc score = 0 (males) or score = 1 (females). Subsequent to this initial step of identifying the low-risk patients, effective stroke prevention (which is essentially OAC) can then be offered to AF patients with ≥1 stroke risk factor(s), with treatment decisions made in consultation with patients and incorporating their preferences. In everyday clinical practice, over 80% of all patients with AF have an indication for OAC, and vascular disease co-exists in ∼30% of them.5–7 With an estimated prevalence of AF of 1–2% and ∼20% of these requiring percutaneous cardiovascular interventions over time,8 ∼1–2 million AF patients in Europe who are …

Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans

Background: We have recently shown that ischemic stroke causes a stress-mediator-induced long-lasting immunodepressive state in mice. Methods: Using head magnetic resonance imaging and standardized immunoassays, we prospectively investigated whether poststroke immunodepression is also seen in humans. Results: Compared to healthy volunteers (n = 30), a rapid depression of lymphocyte counts and a functional deactivation of monocytes and T helper type 1 cells was observed in acute stroke patients (SP; n = 40). Immunodepression was more pronounced in patients with severe clinical deficit or large infarction. On admission the combination of monocytic tumor necrosis factor α release ex vivo and the National Institute of Health Stroke Scale score were the best predictors for nosocomial infection, preferentially affecting older SP. Conclusion: Our data provide evidence for an immediate suppression of cell-mediated immune responses after ischemic stroke in humans.

Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.

Chronic Heart Failure and Ischemic Stroke

Chronic heart failure (CHF) is one of the leading causes of hospitalization, morbidity, and mortality worldwide. This review summarizes current knowledge with regard to CHF as a risk factor for ischemic stroke. CHF is associated with an increased risk of thrombus formation and is accompanied by a 2- to 3-fold increased risk of stroke. Moreover, stroke in CHF patients is associated with poor outcome and higher mortality. Available evidence for additional “vascular” stroke risk factors in heart failure patients is inconsistent and is mostly derived from cohort studies or retrospective analyses. Current guidelines recommend anticoagulation for CHF patients with concomitant atrial fibrillation but not for those in sinus rhythm. Prospective studies are needed to test whether early detection and optimal treatment of CHF reduces the burden of stroke-associated neurologic and neuropsychological sequelae.

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

Left Atrial Catheter Ablation and Ischemic Stroke

Left atrial catheter ablation (LACA) has become an established therapy to abolish drug-refractory symptomatic paroxysmal and persistent atrial fibrillation. Restoring sinus rhythm by LACA may help to prevent atrial fibrillation-related strokes, but presently there is no evidence from randomized clinical trials to support this notion. This review summarizes the current knowledge and uncertainties regarding LACA and procedure-related ischemic stroke. In fact, most patients who undergo LACA have a rather low annual stroke risk even when left untreated, whereas LACA imposes a risk of procedure-related stroke of ≈0.5% to 1%. In addition, LACA may cause cerebral microemboli, resulting in ischemic lesions. These cerebral lesions, detectable by high-resolution MRI, could contribute to neuropsychological deficits and cognitive dysfunction. Furthermore, recurrent atrial fibrillaton episodes can be detected up to years after LACA and might cause ischemic strokes, especially in those patients in whom therapeutic anticoagulation was discontinued. Further prospective multicenter trials are needed to identify procedure-dependent risk factors for stroke and to optimize postprocedural anticoagulation management.

Insular Cortex Lesions, Cardiac Troponin, and Detection of Previously Unknown Atrial Fibrillation in Acute Ischemic Stroke Insights From the Troponin Elevation in Acute Ischemic Stroke Study

Background and Purpose— Detection rates of paroxysmal atrial fibrillation (AF) after acute ischemic stroke increase with duration of ECG monitoring. To date, it is unknown which patient group may benefit most from intensive monitoring strategies. Therefore, we aimed to identify predictors of previously unknown AF during in-hospital ECG monitoring. Methods— All consecutive patients with imaging-confirmed ischemic stroke admitted to our tertiary care hospital from February 2011 to December 2013 were registered prospectively. Patients received continuous bedside ECG monitoring for at least 24 hours. Detection of previously unknown AF during in-hospital ECG monitoring was obtained from medical records. Patients with AF on admission ECG or known history of AF were excluded from analysis. Results— Among 1228 patients (median age, 73 years; median National Institutes of Health Stroke Scale, 4; 43.4% women), previously unknown AF was detected in 114 (9.3%) during a median time of continuous ECG monitoring of 3 days (interquartile range, 2–4 days). Duration of monitoring (P<0.01), older age (P<0.01), history of hypertension (P=0.03), insular cortex involvement (P<0.01), and higher high-sensitivity cardiac troponin T (P=0.04) on admission were independently associated with subsequent detection of AF in a multiple regression analysis. Addition of high-sensitivity cardiac troponin T, insular cortex stroke, or both to the CHADS2 score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke [2P]) significantly improved c-statistics from 0.63 to 0.68 (P=0.01), 0.70 (P<0.01), and 0.72 (P<0.001), respectively. Conclusions— Insular cortex involvement, higher admission high-sensitivity cardiac troponin T, older age, hypertension, and longer monitoring are associated with new detection of AF during in-hospital ECG monitoring. Patients with higher high-sensitivity cardiac troponin T or insular cortex involvement may be candidates for prolonged ECG monitoring.

Troponin elevation in acute ischemic stroke (TRELAS) - protocol of a prospective observational trial

BackgroundLevels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup.Methods/DesignThe primary objective of the prospective observational trial TRELAS (TRoponin ELevation in Acute ischemic Stroke) is to investigate the frequency and underlying pathomechanism of cTnT elevation in acute ischemic stroke patients in order to give guidance for clinical practice. All consecutive patients with acute ischemic stroke admitted within 72 hours after symptom onset to the Department of Neurology at the Campus Benjamin Franklin of the University Hospital Charité will be screened for cTnT elevations (i.e. >= 0.05 μg/l) on admission and again on the following day. Patients with increased cTnT will undergo coronary angiography within 72 hours. Diagnostic findings of coronary angiograms will be compared with age- and gender-matched patients presenting with Non-ST-Elevation myocardial infarction to the Department of Cardiology. The primary endpoint of the study will be the occurrence of culprit lesions in the coronary angiogram indicating underlying co-morbid obstructive coronary artery disease. Secondary endpoints will be the localization of stroke in the cerebral imaging and left ventriculographic findings of wall motion abnormalities suggestive of stroke-induced global cardiac dysfunction.DiscussionTRELAS will prospectively determine the frequency and possible etiology of troponin elevation in a large cohort of ischemic stroke patients. The findings are expected to contribute to clarify pathophysiologic concepts of co-morbid cardiac damage in ischemic stroke patients and also to provide a basis for clinical recommendations for cardiac workup of such patients.Trial registrationclinicaltrials.gov NCT01263964

Prognostic relevance of cardiac troponin T levels and their dynamic changes measured with a high-sensitivity assay in acute ischaemic stroke: analyses from the TRELAS cohort.

BACKGROUND/OBJECTIVES To assess the prognostic relevance of cardiac troponin T (cTnT) values and their serial changes as measured with a high-sensitivity assay in acute ischaemic stroke. METHODS AND RESULTS In total, 1016 consecutive acute ischaemic stroke patients were registered prospectively within a two-year period. High-sensitivity cTnT was quantitated on admission and the following day. Patients were stratified into three groups: below the 99 th percentile of a healthy reference population (< 14 ng/l; n = 409), moderately elevated cTnT (below the median of remaining patients, 14-30 ng/l; n=299) and high cTnT (> 30 ng/l; n = 308). Outcome measures were unfavourable outcome (modified Rankin Scale ≥ 2 at hospital discharge, n=604) and in-hospital mortality (n = 36). Peak cTnT levels were significantly associated with unfavourable outcome (adjusted odds ratios versus reference for moderately elevated cTnT 1.7, 95% confidence interval [CI] 1.1-2.7 and for high cTnT 3.1, 95% CI 1.8-5.6). The optimal cut-off for determining unfavourable outcome proved to be 16 ng/l. Adding this cut-off to clinical variables led to a significant improvement of c-statistics (0.851 versus 0.838, p=0.02). Dynamic changes (δ ≥ 50%) of cTnT were detected in 137 patients (13%). Multiple Cox regression analysis showed an independent association of dynamic changes in cTnT with in-hospital mortality (hazard ratio 2.3, 95% CI 1.1-4.7). The model-fitting (p<0.001) and c-statistics (0.889 versus 0.863, p = 0.08) improved most after dynamic change in cTnT had been added to a regression model which included clinical variables alone. CONCLUSIONS Our study adds novel findings relevant for interpretation of highly sensitive cTnT assays in acute ischaemic stroke: a) Myocardial injury is detectable in more than half of patients; b) even moderately elevated cTnT is associated with unfavourable outcome (optimal cut-off 16 ng/l); and c) dynamic changes in cTnT indicate an increased risk of in-hospital death.

Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting

BACKGROUND Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. METHODS In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam-Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. FINDINGS We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (-0·03 points [4·04]; -0·94 to 0·88; between-group difference Cohens d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. INTERPRETATION 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. FUNDING German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.