Extracardiac findings on coronary computed tomography angiography versus invasive coronary angiography in patients with suspected coronary artery disease and atypical angina

Einleitung: Die koronare Herzkrankheit (KHK) ist eine der häufigsten Ursachen für Morbidität und Mortalität in den Industrienationen, folglich besteht ein hohes sozioökonomisches Interesse an der Erkrankung. Die Goldstandardmethode zur Diagnose der KHK ist nach wie vor die invasive Koronarangiographie (ICA). Darüber hinaus existieren mehrere nicht-invasive Verfahren wie Herz-CT, die ebenfalls zuverlässige Diagnose der KHK ermöglichen. Das primäre Ziel dieser Studie bestand darin, die Detektion der klinisch relevanten extrakardialen Befunde (EKB) bei ICA und CTA zu vergleichen und deren Einfluss auf das Management und Therapie der Patienten mit Verdacht auf KHK zu identifizieren. Methoden: Im Rahmen der randomisiert kontrollierten CAD-Man Studie (Coronary Artery Disease Management) wurden Patienten mit atypischer Angina pectoris und Verdacht auf KHK mittels CTA oder ICA untersucht. In dieser Subanalyse wurden alle durchgeführten Herz-CT und Herzkatheteruntersuchungen (jeweils 167 und 162) hinsichtlich der klinisch relevanten EKB ausgewertet. Im Rahmen der durchgeführten Follow-up Untersuchungen (6-12 Monate, 1-2 Jahre und 3 Jahre nach der initialen Randomisierung) wurden die diagnostischen und eventuellen therapeutischen Maßnahmen evaluiert, die aufgrund der detektierten EKB erfolgt sind. Ergebnisse: Insgesamt wurden 79 klinisch relevante EKB bei 59 Patienten gefunden, darunter bei 55 Patienten, die sich der Herz-CT Untersuchung unterzogen (55/167, 32,9%) und bei 4 Patienten, bei denen die Herzkatheteruntersuchung durchgeführt wurde (4/162, 2,5%). Aufgrund der detektierten EKB wurden insgesamt 38 bildgebende diagnostische Maßnahmen und 34 Facharztüberweisungen bei 59 Patienten angeordnet (CTA: 55; ICA: 4). Bei 17 Patienten folgten therapeutische Maßnahmen (CTA: 16; ICA: 1). Frauen hatten statistisch signifikant häufiger klinisch relevante EKB als Männer. Das Alter und das Rauchverhalten hatten keinen statistisch signifikanten Einfluss auf die Prävalenz von EKB. Fazit: Klinisch relevante EKB werden weitaus häufiger durch CTA als ICA detektiert. Patienten mit atypischer Angina pectoris und Verdacht auf KHK können von einer Herz-CT anstelle einer Herzkatheteruntersuchung profitieren: Erstens durch Detektion der EKB als potenzielle Brutschmerz-verursachende Erkrankungen, zweitens durch Ausschluss einer signifikanten KHK.Introduction: Coronary artery disease (CAD) is one of the most common causes of morbidity and mortality in developed countries, consequently there is a high socioeconomic interest in the disease. The gold standard method for diagnosing CAD is invasive coronary angiography (ICA). Furthermore, several non-invasive methods exist, such as cardiac CT, which also provide reliable diagnosis of CAD. The primary aim of this study was to compare the detection of clinically relevant extracardiac findings (ECF) on ICA and CTA and to identify their impact on the management and therapy of patients with suspected CAD. Methods: In the randomised controlled CAD-Man trial (Coronary Artery Disease Management), patients with atypical angina and suspected CAD were investigated by CTA or ICA. In this subanalysis, all cardiac CTs and cardiac catheterisations performed (167 and 162, respectively) were evaluated regarding the incidence of clinically relevant ECF. During the follow-up examinations (6-12 months, 1-2 years, and 3 years after the initial randomisation), the diagnostic and possible therapeutic measures that were taken due to the detected ECF were evaluated. Results: A total of 79 clinically relevant ECF were found in 59 patients, including 55 patients who underwent cardiac CT (55/167, 32.9%) and 4 patients who underwent cardiac catheterisation (4/162, 2.5%). Based on the detected ECF, a total of 38 diagnostic imaging measures and 34 specialist referrals were ordered in 59 patients (CTA: 55; ICA: 4). Therapeutic measures followed in 17 patients (CTA: 16; ICA: 1). Women had clinically relevant ECF statistically significantly more often than men. Age and smoking behaviour had no statistically significant influence on the prevalence of ECF. Conclusions: Clinically relevant ECF are detected far more frequently by CTA than ICA. Patients with atypical angina and suspected CAD may benefit twofold from undergoing cardiac CT instead of cardiac catheterisation: Firstly, by detecting ECF as potential chest pain-causing conditions, and secondly, by excluding significant CAD

Detection of relevant extracardiac findings on coronary computed tomography angiography vs. invasive coronary angiography

Objectives: To compare the detection of relevant extracardiac findings (ECFs) on coronary computed tomography angiography (CTA) and invasive coronary angiography (ICA) and evaluate the potential clinical benefit of their detection. Methods: This is the prespecified subanalysis of ECFs in patients presenting with a clinical indication for ICA based on atypical angina and suspected coronary artery disease (CAD) included in the prospective single-center randomized controlled Coronary Artery Disease Management (CAD-Man) study. ECFs requiring immediate therapy and/or further workup including additional imaging were defined as clinically relevant. We evaluated the scope of ECFs in 329 patients and analyzed the potential clinical benefit of their detection. Results: ECFs were detected in 107 of 329 patients (32.5%; CTA: 101/167, 60.5%; ICA: 6/162, 3.7%; p < .001). Fifty-nine patients had clinically relevant ECFs (17.9%; CTA: 55/167, 32.9%; ICA: 4/162, 2.5%; p < .001). In the CTA group, ECFs potentially explained atypical chest pain in 13 of 101 patients with ECFs (12.9%). After initiation of therapy, chest pain improved in 4 (4.0%) and resolved in 7 patients (6.9%). Follow-up imaging was recommended in 33 (10.0%; CTA: 30/167, 18.0%; ICA: 3/162, 1.9%) and additional clinic consultation in 26 patients (7.9%; CTA: 25/167, 15.0%; ICA: 1/162, 0.6%). Malignancy was newly diagnosed in one patient (0.3%; CTA: 1/167, 0.6%; ICA: 0). Conclusions: In this randomized study, CTA but not ICA detected clinically relevant ECFs that may point to possible other causes of chest pain in patients without CAD. Thus, CTA might preclude the need for ICA in those patients

The Distribution of Glucosinolates in Different Phenotypes of Lepidium peruvianum and Their Role as Acetyl- and Butyrylcholinesterase Inhibitors&mdash;In Silico and In Vitro Studies

The aim of the study was to present the fingerprint of different Lepidium peruvianum tuber extracts showing glucosinolates-containing substances possibly playing an important role in preventinting dementia and other memory disorders. Different phenotypes of Lepidium peruvianum (Brassicaceae) tubers were analysed for their glucosinolate profile using a liquid chromatograph coupled with mass spectrometer (HPLC-ESI-QTOF-MS/MS platform). Qualitative analysis in 50% ethanolic extracts confirmed the presence of ten compounds: aliphatic, indolyl, and aromatic glucosinolates, with glucotropaeolin being the leading one, detected at levels between 0&ndash;1.57% depending on phenotype, size, processing, and collection site. The PCA analysis showed important variations in glucosinolate content between the samples and different ratios of the detected compounds. Applied in vitro activity tests confirmed inhibitory properties of extracts and single glucosinolates against acetylcholinesterase (AChE) (15.3&ndash;28.9% for the extracts and 55.95&ndash;57.60% for individual compounds) and butyrylcholinesterase (BuChE) (71.3&ndash;77.2% for the extracts and 36.2&ndash;39.9% for individual compounds). The molecular basis for the activity of glucosinolates was explained through molecular docking studies showing that the tested metabolites interacted with tryptophan and histidine residues of the enzymes, most likely blocking their active catalytic side. Based on the obtained results and described mechanism of action, it could be concluded that glucosinolates exhibit inhibitory properties against two cholinesterases present in the synaptic cleft, which indicates that selected phenotypes of L. peruvianum tubers cultivated under well-defined environmental and ecological conditions may present a valuable plant material to be considered for the development of therapeutic products with memory-stimulating properties

Cyclolization of D-Lysergic Acid Alkaloid Peptides

The tripeptide chains of the ergopeptines, a class of pharmacologically important D-lysergic acid alkaloid peptides, are arranged in a unique bicyclic cyclol based on an amino-terminal α-hydroxyamino acid and a terminal orthostructure. D-lysergyl-tripeptides are assembled by the nonribosomal peptide synthetases LPS1 and LPS2 of the ergot fungus Claviceps purpurea and released as N-(D-lysergyl-aminoacyl)-lactams. We show total enzymatic synthesis of ergopeptines catalyzed by a Fe²⁺/2-ketoglutarate-dependent dioxygenase (EasH) in conjunction with LPS1/LPS2. Analysis of the reaction indicated that EasH introduces a hydroxyl group into N-(D-lysergyl-aminoacyl)-lactam at α-C of the aminoacyl residue followed by spontaneous condensation with the terminal lactam carbonyl group. Sequence analysis revealed that EasH belongs to the wide and diverse family of the phytanoyl coenzyme A hydroxylases. We provide a high-resolution crystal structure of EasH that is most similar to that of phytanoyl coenzyme A hydroxylase, PhyH, from human