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ZusammenfassungDas Takotsubo Syndrom (TTS) ist gekennzeichnet durch akut auftretende transiente Wandbewegungsstörungen des linken Ventrikels, denen angiografisch keine signifikanten Koronarstenosen zugrunde liegen. Die Erkrankung tritt überwiegend bei älteren Frauen in der Menopause auf, prinzipiell können jedoch Patienten jeden Alters und beiderlei Geschlechts betroffen sein. Insgesamt wird bei etwa 2% aller Patienten mit dem Verdacht auf ein akutes Koronarsyndrom (ACS) die Diagnose eines TTS gestellt; bei Frauen mit ACS-Verdacht liegt die Inzidenz mit 6–9% deutlich höher. Als Triggerfaktor für ein TTS findet sich bei Frauen häufiger emotionaler Stress und bei Männern physischer Stress. Im Akutstadium der Erkrankung können schwerwiegende Komplikationen auftreten, die Krankenhausmortalität ist vergleichbar mit der beim akuten Myokardinfarkt und bei Männern infolge von Begleiterkrankungen höher als bei Frauen mit einem TTS. Aktuell existiert keine evidenzbasierte Therapie. Um die Prognose des TTS im Akutstadium verbessern und Rezidive verhindern zu können, sind prospektive randomisierte Studien erforderlich.

In randomized trials, direct oral anticoagulants (DOAC) were non-inferior to the vitamin-K-antagonist (VKA) warfarin in preventing stroke/embolism in patients with atrial fibrillation (AF). DOAC are substrates for P-glycoprotein (P-gp), CYP3A4 and CYP2C9. The activity of these enzymes is modulated by several drugs which might induce pharmacokinetic drug-drug interactions (DDI). Drugs affecting platelet function have the potential for pharmacodynamic DDI of DOAC. The literature was searched for: ‘dabigatran,’ ‘rivaroxaban,’ ‘edoxaban,’ or ‘apixaban’ and drugs affecting platelet function, CYP3A4-, CYP2C9- or P-gp-activity. Reports about bleeding and embolic events attributed to DDI with DOAC in AF-patients were found for 43 of 171 drugs with interacting potential (25%), most frequently with antiplatelet and nonsteroidal anti-inflammatory drugs. Whereas a co-medication of platelet-affecting drugs is invariably reported to increase the bleeding risk, the findings regarding P-gp-, CYP3A4- and CYP2C9- activity-affecting drugs are ambiguous. Tests for plasma DOAC-levels and information about DDI of DOAC should be widely available and user-friendly. If advantages and disadvantages of DOAC and VKA can be investigated exhaustively, individualized anticoagulant therapy can be offered to patients, considering co-medication, comorbidities, genetic and geographic factors and the health care system.

Introduction: In patients with cerebral amyloid angiopathy (CAA), intracerebral hemorrhage (ICH) and atrial fibrillation (AF), both antiplatelet and anticoagulant therapy for prevention of embolic stroke increases the risk of recurrent intracerebral hemorrhage. Left atrial appendage closure (LAAC) has, therefore, been suggested as an alternative to antithrombotic therapy in patients with CAA.Case description: A man in his mid-80s suffered from ICH and CAA was diagnosed by magnetic resonance imaging of the brain. He had a history of arterial hypertension, dyslipidemia, monoclonal gammopathy (IgG kappa), and chronic obstructive pulmonary disease. Four months previously, edoxaban 60 mg/d had been prescribed because of permanent AF. Blood pressure at admission was 170/80 mm Hg. The NT-pro-BNP level was 1819 ng/L (reference value: < 486 ng/L). The electrocardiogram showed AF. Echocardiography showed an enlarged left atrium, left ventricular wall thickening, good systolic function and diastolic dysfunction. Edoxaban was stopped and the ICH resolved within 16 days. Interventional LAAC was considered but eventually not performed because of the following reasons: 1. Postinterventional antiplatelet therapy to prevent device-associated thrombus formation would expose him to the risk of recurrent ICH. 2. Aggravation of heart failure may occur due to the missing hemodynamic and endocrine properties of the left atrial appendage. Thus, optimization of antihypertensive therapy without any antiplatelet or anticoagulant therapy was recommended. Thirteen months after ICH, no further hemorrhagic or ischemic events had occurred. Conclusion: In view of the lack of randomized clinical trials in patients with CAA, ICH and AF, neither LAAC nor anticoagulant nor antiplatelet therapy but a healthy lifestyle with a blood-pressure target of < 120/80 mmHg should be recommended to prevent recurrent ICH.

This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including β-adrenergic receptor signalling, G-protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:24 issue:2 pages:257-273 ispartof: location:England status: published