[Morphological and functional diagnostics of coronary artery disease by computed tomography]. / Morphologische und funktionelle Diagnostik der koronaren Herzkrankheit mittels Computertomographie.

Computed tomography coronary angiography (cCTA) is a safe option for the noninvasive exclusion of significant coronary stenoses in patients with a low or moderate pretest probability for coronary artery disease (CAD). Furthermore, it also allows functional and morphological assessment of coronary stenoses. The European Society of Cardiology (ESC) guidelines on the diagnosis and management of chronic coronary syndrome published in 2019 have strengthened the importance of cCTA in this context and for this reason it has experienced a considerable upgrade. The determination of the Agatston score is a clinically established method for quantifying coronary calcification and influences the initiation of drug treatment. With technologies, such as the introduction of electrocardiography (ECG)-controlled dose modulation and iterative image reconstruction, cCTA can be performed with high image quality and low radiation exposure. Anatomic imaging of coronary stenoses alone is currently being augmented by innovative techniques, such as myocardial CT perfusion imaging or CT-fractional flow reserve (FFR) but the clinical value of these methods merits further investigation. The cCTA could therefore develop into a gatekeeper with respect to the indications for invasive coronary diagnostics and interventions.

[Factors influencing the choice of androgen deprivation therapy for patients with hormone-sensitive prostate cancer : Results of the ProComD study]. / Einflussfaktoren bei der Wahl der Androgendeprivationstherapie für Patienten mit hormonsensitiven Prostatakarzinom : Ergebnisse der ProComD-Studie.

BACKGROUND: Androgen deprivation therapy (ADT) with a GnRH agonist or the GnRH antagonist degarelix is a central component in the treatment of prostate cancer (PCa). Little is currently known regarding the decision criteria. Knowledge of these could improve the success of treatment in the future. OBJECTIVES: To identify factors influencing the treatment decision in patients with hormone-sensitive prostate cancer receiving ADT and to determine the incidence of concomitant disease in both treatment groups. METHODS: The two-arm, prospective, non-interventional study "ProComD" was conducted from September 2014 to June 2019 at 80 study centers in Germany. After the therapy decision was made, patients with hormone-sensitive prostate cancer needing ADT were included in the study. Data were collected during routine visits. RESULTS: Data from 413 patients were evaluated (degarelix N = 268; GnRH agonists N = 145). Key factors influencing the therapy decision for both treatment options included comorbidities (42% of all patients), compliance (64%), and age (81%). The source of information consulted most frequently regarding existing comorbidities was the patient's medical history conducted by the treating urologist themselves (65% in both groups). For patients with pre-existing cardiovascular diseases, the doctor's letter (45.8% degarelix vs. 38.9% GnRH agonists) or the medical history questionnaire (38.9% degarelix vs. 20% GnRH agonists) was additionally taken into account. CONCLUSION: Comorbidities along with age and compliance are among the key factors influencing the treatment decisions made by urologists.

Recurrence of atrial fibrillation after pulmonary vein isolation in dependence of arterial stiffness.

BACKGROUND: Arterial stiffness (AS) has emerged as a strong predictor of cardiovascular (CV) diseases. Although increased AS has been described as a predictor of atrial fibrillation (AF), its role as a risk marker for AF recurrence has not yet been elucidated. METHODS: Patients with AF who underwent pulmonary vein isolation (PVI) were included in this study. Presence of AS was evaluated by measuring aortic distensibility (AD) of the descending aorta by transoesophageal echocardiography. RESULTS: In total, 151 patients (mean ± standard deviation (SD) age 71.9 ± 9.8 years) were enrolled and followed for a median duration of 21 months (interquartile range 15.0-31.0). During follow-up, AF recurred in 94 (62.3%) patients. AF recurrence was seen more frequently in patients with permanent AF (27% vs 46%, p = 0.03) and in those who had undergone prior PVI (9% vs 23%, p = 0.02). AD was significantly reduced in patients with AF recurrence (mean ± SD 2.6 ± 2.3 vs 1.5 ± 0.7â€¯× 10-3 mm Hg-1, p < 0.0001), as well as left atrial volume index (LAVI) (mean ± SD 29 ± 12 vs 44 ± 15 ml/m2, p < 0.0001). Multivariable analysis revealed LAVI (odds ratio (OR) 2.9, 95% confidence interval (CI) 1.2-3.4) and AS (OR 3.6, 95% CI 2.8-4.1) as independent risk factors of AF recurrence. CONCLUSION: Increased AS and left atrial size were independent predictors of AF recurrence after PVI. AD as surrogate marker of AS seemed to reflect the overall CV risk. In addition, AD was significantly correlated with left atrial size, which suggests that increased AS leads to atrial remodelling and thus to AF recurrence. TRIAL REGISTRATION: German registry for clinical studies (DRKS), DRKS00019007.

[Troponin elevation in acute ischemic stroke-unspecific or acute myocardial infarction? : Diagnostics and clinical implications]. / Troponinerhöhung beim akuten ischämischen Schlaganfall ­ unspezifisch oder Ausdruck eines akuten Myokardinfarkts? : Diagnostik und klinische Implikationen.

Routine determination of troponin levels is recommended for all patients with acute ischemic stroke. In 20-55% of these patients the troponin levels are elevated, which may be caused by ischemic as well as non-ischemic myocardial damage and particularly neurocardiogenic myocardial damage. In patients with acute ischemic stroke, the prevalence of previously unknown coronary heart disease is reported to be up to 27% and is prognostically relevant for these patients; however, relevant coronary stenoses are less frequently detected in stroke patients with troponin elevation compared to patients with non-ST elevation myocardial infarction. The risk of secondary intracerebral hemorrhage due to the necessity for dual platelet aggregation inhibition illustrates the challenging indication for invasive coronary diagnostics and revascularization. Therefore, a diagnostic work-up and interdisciplinary risk evaluation appropriate to the urgency are necessary in order to be able to determine a reasonable treatment approach with timing of the intervention, type and duration of blood thinning. In addition to conventional examination methods, multimodal cardiac imaging is increasingly used for this purpose. This review article aims to provide a pragmatic and clinically oriented approach to diagnostic and therapeutic procedures, taking into account the available evidence.

[ARENA-Project atrial fibrillation in the Rhein-Neckar region]. / ARENA ­ Projekt Vorhofflimmern in der Rhein-Neckar-Region.

Atrial fibrillation (AF) is the most common form of cardiac tachyarrhythmia. It is estimated that in the Rhein-Neckar region approximately 40,000-50,000 out of 2 million people are affected. Due to demographic changes in the near future there will be a significant increase in the prevalence of AF within the next decades. The ARENA project was initiated by the Foundation Institute for Cardiac Infarction Research (IHF) Ludwigshafen in cooperation with cardiological and neurological departments of neighboring hospitals, resident doctors and pharmacies to improve the awareness and care of patients with AF. The particular aim is the prevention of stroke as one of the most dreaded complications. The project focusses on the following three subtopics: interventions, medication, migration. The aim of the intervention project is to raise awareness of AF as a risk factor for stroke and to improve the diagnostic work-up and care for patients with diagnosed or unknown AF. The subproject medication focusses on the adherence of patients with AF to the prescribed antithrombotic medication. To evaluate differences concerning patients with and without a migration background the subproject migration was initiated.

Do obstetricians apply the national guidelines? A vignette-based study assessing practices for the prevention of preterm birth.

OBJECTIVE: To describe spontaneous preterm birth prevention practices self-reported before and after the dissemination of relevant guidelines, and to identify personal and organisational factors associated with adherence. DESIGN: A repeated cross-sectional vignette-based survey study. SETTING: French obstetricians. POPULATION: French obstetricians practicing in public or private maternity units. METHODS: Before and after the dissemination of the 2017 French guidelines on the prevention of spontaneous preterm birth, participants were asked to complete a web-based self-administered questionnaire based on two clinical vignettes. Vignette 1 focused on respondents' attitudes towards strict bed rest, cerclage, and progesterone treatment for women with a short cervix in mid-trimester; vignette 2 focused on attitudes towards strict bed rest and maintenance tocolysis after successful tocolysis for preterm labour. A mixed quantitative and qualitative analysis was conducted. MAIN OUTCOME MEASURES: Non-adherence to guidelines for the prevention of spontaneous preterm birth in responses to each vignette. RESULTS: We obtained complete responses from 286 obstetricians before and 282 obstetricians after guideline dissemination, including 145 obstetricians participating in both. After dissemination, 51.4% of obstetricians self-reported non-adherent practices for vignette 1 and 22.3% of obstetricians self-reported non-adherent practices for vignette 2. No improvement was observed after dissemination. The quantitative analysis identified factors associated with non-adherence, including older age and practice in non-university or small hospitals, whereas the qualitative analysis highlighted barriers to implementation, including fear of change, habits, work overload, and lack of time. CONCLUSIONS: Adherence to guidelines was generally low, with practices unmodified by their dissemination. Improvement is required, especially regarding applicability. TWEETABLE ABSTRACT: Adherence to guidelines to prevent spontaneous preterm birth was generally low and remained unmodified after guideline dissemination.

[Breech Presentation: CNGOF Guidelines for Clinical Practice - Short Text]. / Présentation du siège. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

OBJECTIVES: To determine the optimal management of singleton breech presentation. MATERIALS AND METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: In France, 5% of women have breech deliveries (Level of Evidence [LE3]). One third of them have a planned vaginal delivery (LE3) of whom 70% deliver vaginally (LE3). External cephalic version (ECV) is associated with a reduced rate of breech presentation at birth (LE2), and with a lower rate of cesarean section (LE3) without increases in severe maternal (LE3) and perinatal morbidity (LE3). It is therefore recommended to inform women with a breech presentation at term that ECV could be attempted from 36 weeks of gestation (Professional consensus). In case of breech presentation, planned vaginal compared with planned cesarean delivery might be associated with an increased risk of composite perinatal mortality or serious neonatal morbidity (LE2). No difference has been found between planned vaginal and planned cesarean delivery for neurodevelopmental outcomes at two years (LE2), cognitive and psychomotor outcomes between 5 and 8 years (LE3), and adult intellectual performances (LE4). Short and long term maternal complications appear similar in case of planned vaginal compared with planned cesarean delivery in the absence of subsequent pregnancies. A previous cesarean delivery results for subsequent pregnancies in higher risks of uterine rupture, placenta accreta spectrum and hysterectomy (LE2). It is recommended to offer women who wish a planned vaginal delivery a pelvimetry at term (Grade C) and to check the absence of hyperextension of the fetal head by ultrasonography (Professional consensus) to plan their mode of delivery. Complete breech presentation, previous cesarean, nulliparity, term prelabor rupture of membranes do not contraindicate planned vaginal delivery (Professionnal consensus). Term breech presentation is not a contraindication to labor induction when the criteria for acceptance of vaginal delivery are met (Grade C). CONCLUSION: In case of breech presentation at term, the risks of severe morbidity for the child and the mother are low after both planned vaginal and planned cesarean delivery. For the French College of Obstetricians and Gynecologists (CNGOF), planned vaginal delivery is a reasonable option in most cases (Professional consensus). The choice of the planned route of delivery should be shared by the woman and her caregiver, respecting the right to woman's autonomy.

[Bedside implantation of a new temporary vena cava inferior filter : German results from the European ANGEL registry]. / Bettseitige Implantation eines neuen passageren V.-cava-inferior-Filters : Deutsche Daten aus dem europäischen ANGEL-Register.

BACKGROUND: Pulmonary embolism (PE) is a frequently occurring complication in critically ill patients, and the simultaneous occurrence of PE and life-threatening bleeding is a therapeutic dilemma. Inferior vena cava filters (IVCF) may represent an important therapeutic alternative in these cases. The Angel® catheter (Bio2 Medical Inc., San Antonio, TX, USA) is a novel IVCF that provides temporary protection from PE and is implanted at bedside without fluoroscopy. MATERIAL AND METHODS: The European Angel® Catheter Registry is an observational, multicenter study. In our German substudy, we investigated patients from three German hospitals and four intensive care units, who underwent Angel® catheter implantation between February 2016 and December 2016. RESULTS: A total of 23 critically ill patients (68 ± 9 years, 43% male) were included. The main indication for implantation was a high risk for or an established PE, combined with contraindications for prophylactic or therapeutic anticoagulation due to either an increased risk of bleeding (81%) or active bleeding (13%). The Angel® catheter was successfully inserted in all patients at bedside. No PE occurred in patients with an indwelling Angel® catheter. Clots with a diameter larger the 20 mm, indicating clot migration, were detected in 5% of the patients by cavography before filter retrieval. Filter retrieval was uneventful in all of our cases, while filter dislocation occurred in 3% of the patients. CONCLUSION: The German data from the multicenter European Angel® Catheter Registry show that the Angel® catheter is a safe and effective approach for critically ill patients with a high risk for the development of PE or an established PE, when an anticoagulation therapy is contraindicated.

Pitfalls in accelerometer-based measurement of physical activity: The presence of reactivity in an adult population.

When a behavior is monitored, it is likely to change, even if no change may be intended. This phenomenon is known as measurement reactivity. We investigated systematic changes in accelerometer-based measures over the days of monitoring as an indicator of measurement reactivity in an adult population. One hundred seventy-one participants from the general population (65% women; mean age = 55 years, range: 42-65 years) wore accelerometers for 7 consecutive days to measure sedentary behavior and physical activity (PA). Latent growth models were used (a) to investigate changes in accelerometer wear time over the measurement days and (b) to identify measurement reactivity indicated by systematic changes in sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Over the measurement days, participants reduced accelerometer wear time by trend (rate of change [b] = -4.7 min/d, P = .051, Cohen's d = .38), increased ST (b = 2.4 min/d, P = .018, d = .39), and reduced LPA (b = -2.4 min/d, P = .015, d = .38). Participants did not significantly reduce MVPA (P = .537). Our data indicated that accelerometry might generate reactivity. Small effects on ST and LPA were found. Thus, the validity of accelerometer-based data on ST and LPA may be compromised. Systematic changes observed in accelerometer wear time may further bias accelerometer-based measures. MVPA seems to be less altered due to the presence of an accelerometer.

[Instantaneous wave-free ratio (iFR®) in patients with coronary artery disease]. / "Instantaneous wave-free ratio" (iFR®) bei Patienten mit koronarer Herzkrankheit.

Coronary angiography is considered as the gold standard in the morphological representation of coronary artery stenosis. Coronary angiography is often performed without preprocedural non-invasive proof of ischemia and the assessment of the severity of a coronary lesion by morphology is very subjective. Thus, invasive fractional flow reserve (FFR) measurement represents the current standard for estimation of the hemodynamic relevance of coronary artery stenosis and facilitates decision making for percutaneous coronary intervention (PCI) and stenting. The FFR-guided revascularization strategy has been classified as a class IA recommendation in the 2014 ESC/EACTS guidelines on myocardial revascularization. Both the DEFER and the FAME studies showed no treatment advantage of hemodynamically irrelevant stenosis. By use of FFR (and targeted interventions), clinical results could be improved as well as the procedure costs were reduced; however, the use in clinical practice is still limited due to the need of adenosine administration and a significant prolongation of the procedure. Instantaneous wave-free ratio (iFR®) is a new innovative approach for the determination of the hemodynamic relevance of coronary stenosis which can be obtained at rest without the use of vasodilators. Regarding periprocedural complications as well as prognosis, iFR® showed non-inferiority compared to FFR in the SWEDEHEART and DEFINE-FLAIR trials.

Correction to: Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism.

The article Occlusion of left atrial appendage aff ects metabolomic profile:focus on glycolysis, tricarboxylic acid and urea metabolism, written by K. Sattler, M. Behnes, C. Barth, A. Wenke, B. Sartorius, I. El-Battrawy, K. Mashayekhi, J. Kuschyk, U. Hoffmann, T. Papavasiliu, C. Fastner, S. Baumann, S. Lang, X. Zhou, G. Yücel, M. BorggrefeI, Akin, was originally published Online First without open access.

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism.

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet. OBJECTIVES: We aimed to study the effects of interventional LAAC on systemic metabolism. METHODS: Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1). RESULTS: During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta -0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01). CONCLUSIONS: Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

[Computed tomography in patients with chronic stable angina : Fractional flow reserve measurement]. / Computertomographie bei Patienten mit stabiler Angina Pectoris : Messung der fraktionellen Flussreserve.

Coronary computed tomography angiography (cCTA) has been established for the non-invasive diagnosis of coronary artery disease (CAD). Previous studies demonstrated the high diagnostic accuracy of cCTA, particularly for ruling out CAD. As a known limitation of cCTA a large number of visually significant coronary stenoses are found to be hemodynamically not relevant by invasive fractional flow reserve (FFR). CT-based FFR (CT-FFR) builds on recent advances in computational fluid dynamics and image simulation techniques. Along with CT myocardial perfusion imaging, CT-FFR is a promising approach towards a more accurate estimation of the hemodynamic relevance of coronary artery stenoses. CT-FFR is derived from regular CT datasets without additional image acquisitions, contrast material, or medication. Two CT-FFR techniques can be differentiated. The initial method requires external use of supercomputers and has gained approval for clinical use in the USA. Furthermore, a prototype-software has been introduced which is less computationally demanding via integration of reduced-order models for on-site calculation of CT-FFR. The present article reviews these methods in the context of available study results and meta-analyses. Furthermore, limitations and future concepts of CT-FFR are discussed.

[Acute pulmonary embolism and contraindication of anticoagulation : Bedside implantation of a new temporary vena cava inferior filter]. / Akute Lungenembolie und Kontraindikation für eine Antikoagulation : Bettseitige Implantation eines neuen passageren V.-cava-inferior-Filters.

Pulmonary embolism (PE), mostly caused by deep vein thrombosis, is a life-threatening complication in critically ill patients in the intensive care unit. A potential strategy to prevent PE in patients with contraindication for anticoagulant therapy is the implantation of a vena cava filter (VCF), to provide fast and safe PE protection against ascending thrombi. We report the case of a 56-year-old woman with an intracranial hemorrhage, who developed a PE. Because of acute contraindications for anticoagulant therapy, bedside implantation of a new VCF was performed to overcome the period of absolute contraindications for anticoagulation. After explanation, several thrombi were found on the filter.

Live cell imaging of septin dynamics in Ustilago maydis.

Septins are highly conserved cytoskeletal proteins involved in a variety of biological processes such as cell polarization and cytokinesis. In humans, functional defects in these proteins have been linked to cancer and neuronal diseases. In recent years, substantial progress has been made in studying the structure of septin subunits and the formation of defined heteromeric building blocks. These are assembled into higher-order structures at distinct subcellular sites. An important microscopic approach in studying septin assembly and dynamics is the use of septins tagged with fluorescent proteins. This revealed, eg, that septins form rings during cytokinesis and that septins build extended filaments partially colocalizing with actin cables and microtubules. Here, we describe extensive live cell imaging of septins in the model microorganism Ustilago maydis. We present techniques to study dynamic localization of protein and septin mRNA on shuttling endosomes as well as colocalization of proteins at these highly motile units. Moreover, FLIM-FRET experiments for analyzing local protein interactions are presented. Importantly, these imaging approaches transfer well to other fungal and animal model systems for in vivo analysis of septin dynamics.

Comparison and outcome analysis of patients with apical and non-apical takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is a relevant differential diagnosis in patients presenting with signs of an acute coronary syndrome. Although recent literature has highlighted some salient features of this disorder, there has been little information elucidating the differences in clinical features, electrocardiographic findings, echocardiographic data and TTC-related complications associated with the different variants of TTC. METHODS AND RESULTS: Our institutional database constituted a collective of 114 patients diagnosed with TTC between 2003 and 2015 and these patients were subsequently divided into two groups based on the presence (n = 82, 72%) or absence (n = 32, 28%) of the apical form of TTC. The protocol for our proposed study was approved by the Ethics Committee of the University Medical Centre in Mannheim. It was noticed that the patients presenting with the apical form of TTC belonged to an older age group as compared to those presenting with the non-apical form (61.1 ± 8.9 years vs. 69.5 ± 11.2; P < 0.01). The QTc interval prolongation at index-event was observed to be quantifiably greater in the 'apical variant' patients group (484.8 ± 57 ms vs. 464 ± 34.1 ms; P = 0.06). With respect to cardiovascular risk factors, patients with arterial hypertension did have a higher predilection to present with the apical form (63.4% vs. 43.7%; P = 0.06), however, the impact of smoking was less pronounced in this patient group (24.4% vs. 50%, P = 0.01). Furthermore, our study highlighted a significant impact on ejection fraction (EF), with a compromised left ventricular function (36 ± 9% vs. 42.4 ± 9.7%, P < 0.01) and greater involvement of the right ventricle in the apical variant patients group (23% vs. 3%, P = 0.04). Patients with the apical form also showed a greater tendency to develop TTC-related complications such as cardiogenic shock and required longer monitoring and care in comparison. CONCLUSIONS: The apical and non-apical variants of TTC are manifestations of the same syndrome. They differ significantly, however, in their clinical presentation, related complications and prognosis.

Photodeoxygenation of dinaphthothiophene, benzophenanthrothiophene, and benzonaphthothiophene S-oxides.

Photoinduced deoxygenation of dibenzothiophene S-oxide (DBTO) has been suggested to release atomic oxygen [O((3)P)]. To expand the conditions and applications where O((3)P) could be used, generation of O((3)P) at longer wavelengths was desirable. The sulfoxides benzo[b]naphtho-[1,2,d]thiophene S-oxide, benzo[b]naphtho[2,1,d]thiophene S-oxide, benzo[b]phenanthro[9,10-d]thiophene S-oxide, dinaphtho[2,1-b:1',2'-d]thiophene S-oxide, and dinaphtho[1,2-b:2',1'-d]thiophene S-oxide all absorb light at longer wavelengths than DBTO. To determine if these sulfoxides could be used to generate O((3)P), quantum yield studies, product studies, and computational analysis were performed. Quantum yields for the deoxygenation were up to 3 times larger for these sulfoxides compared to DBTO. However, oxidation of the solvent by these sulfoxides resulted in different ratios of oxidized products compared to DBTO, which suggested a change in deoxygenation mechanism. Density functional calculations revealed a much larger singlet-triplet gap for the larger sulfoxides compared to DBTO. This led to the conclusion that the examined sulfoxides could undergo deoxygenation by two different mechanisms.