Artificial intelligence models in prediction of response to cardiac resynchronization therapy: a systematic review.

The aim of the presented review is to summarize the literature data on the accuracy and clinical applicability of artificial intelligence (AI) models as a valuable alternative to the current guidelines in predicting cardiac resynchronization therapy (CRT) response and phenotyping of patients eligible for CRT implantation. This systematic review was performed according to the PRISMA guidelines. After a search of Scopus, PubMed, Cochrane Library, and Embase databases, 675 records were identified. Twenty supervised (prediction of CRT response) and 9 unsupervised (clustering and phenotyping) AI models were analyzed qualitatively (22 studies, 14,258 patients). Fifty-five percent of AI models were based on retrospective studies. Unsupervised AI models were able to identify clusters of patients with significantly different rates of primary outcome events (death, heart failure event). In comparison to the guideline-based CRT response prediction accuracy of 70%, supervised AI models trained on cohorts with > 100 patients achieved up to 85% accuracy and an AUC of 0.86 in their prediction of response to CRT for echocardiographic and clinical outcomes, respectively. AI models seem to be an accurate and clinically applicable tool in phenotyping of patients eligible for CRT implantation and predicting potential responders. In the future, AI may help to increase CRT response rates to over 80% and improve clinical decision-making and prognosis of the patients, including reduction of mortality rates. However, these findings must be validated in randomized controlled trials.

Circadian rhythm of brain-derived neurotrophic factor in serum and plasma.

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments.

Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline.

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p < 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p < 0.001, ηp2 = 0.581) and plasma (p < 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Analysis of a nurse-provided on-call peritoneal dialysis support in an outpatient reference care centre.

BACKGROUND: To analyse the nature of medical or technical emergency issues of ambulatory peritoneal dialysis (PD) patients calling a nurse-provided emergency PD support service of a reference centre that is provided all year in the after-hours. METHODS: We retrospectively analysed patients' chief complaint, urgency, resolution of and association to current PD treatment and modality directed to an on-call nurse-provided PD support service from 2015-2021 based on routinely collected health data. Calls were systematically categorized being technical/procedural-, medical-, material-related or type of correspondence. Call urgency was categorized to have "immediate consequence", inquiry was eligible for "processing next working day" or whether there was "no need for further action". Call outcomes were classified according to whether patients were able to initiate, resume or finalize their treatments or whether additional interventions were required. Unexpected adverse events such as patients' acute hospitalization or need for nurses' home visits were evaluated and quantified. RESULTS: In total 753 calls were documented. Most calls were made around 7:30 a.m. (5:00-9:00; median, 25-75th CI) and 6:30 p.m. (5:00-8:15). 645 calls were assigned to continuous ambulatory- (CAPD) or automated PD (APD). Of those, 430 calls (66.7%) had an "immediate consequence". Of those 77% (N = 331) were technical/procedural-, 12.8% (N = 55) medical- and 6.3% (N = 27) material related issues. 4% (N = 17) were categorized as other correspondence. Issues disrupting the course of PD were identified in 413 cases. In 77.5% (N = 320) patients were able to initiate, resume or finalize their treatment after phone consultation. Last-bag exchange was used in 6.1% enabling continued therapy in 83.6%. In 35 cases a nurse visit at patients' home or patients' visit to the practice at the earliest possible date were required, while hospitalization was required in seven medical category cases (5.4% and 1.09% of total assessed calls, respectively). CONCLUSION: The on-call PD-nurse provides patient support for acute and imminent issues enabling them to successfully initiate, resume or finalize their prescribed treatment. Nurses triage of acute conditions facilitated rapid diagnostics and therapy. Maintaining quality PD homecare, the provision of trained personnel is indispensable. The information gathered in this study may therefore be used as a foundation to tailor educational programs for nephrology nurses and doctors to further develop their competencies in PD.

Catheter navigation by intracardiac echocardiography enables zero-fluoroscopy linear lesion formation and bidirectional cavotricuspid isthmus block in patients with typical atrial flutter.

INTRODUCTION: One of the most helpful aspects of intracardiac echocardiography (ICE) implementation in electrophysiological studies (EPS) is the real-time visualisation of catheters and cardiac structures. In this prospective study, we investigated ICE-guided zero-fluoroscopy catheter navigation during radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) in patients with typical atrial flutter (AFL). METHODS AND RESULTS: Thirty consecutive patients (mean age 72.9 ± 11.4 years, 23 male) with ongoing (n = 23) or recent CTI-dependent AFL underwent an EPS, solely utilizing ICE for catheter navigation. Zero-fluoroscopy EPS could be successfully accomplished in all patients. Mean EPS duration was 41.4 ± 19.9 min, and mean ablation procedure duration was 20.8 ± 17.1 min. RF ablation was applied for 6.0 ± 3.1 min (50W, irrigated RF ablation). Echocardiographic parameters, such as CTI length, prominence of the Eustachian ridge (ER), and depth of the CTI pouch on the ablation plane, were assessed to analyse their correlation with EPS- or ablation procedure duration. The CTI pouch was shallower in patients with an ablation procedure duration above the median (4.8 ± 1.1 mm vs. 6.4 ± 0.9 mm, p = 0.04), suggesting a more lateral ablation plane in these patients, where the CTI musculature is stronger. CTI length or ER prominence above the respective median did not correlate with longer EPS duration. CONCLUSIONS: Zero-fluoroscopy CTI ablation guided solely by intracardiac echocardiography in patients with CTI-dependent AFL is feasible and safe. ICE visualisation may help to localise the optimal ablation plane, detect and correct poor tissue contact of the catheter tip, and recognise early potential complications during the ablation procedure.

A Molecular Biomarker-Based Triage Approach for Targeted Treatment of Post-COVID-19 Syndrome Patients with Persistent Neurological or Neuropsychiatric Symptoms.

Approximately 30% of COVID-19 cases may experience chronic symptoms, known as post-COVID-19 syndrome (PCS). Common PCS symptoms can include fatigue, cognitive impairment, and persistent physical, neurological, and neuropsychiatric complaints. To improve healthcare and management of the current and future pandemics, we highlight the need for establishing interdisciplinary post-viral outpatient clinics comprised of specialists in fields such as psychiatry, psychotherapy, neurology, cardiology, pneumology, and immunology. In this way, PCS patients with a high health burden can receive modern diagnostics and targeted therapeutic recommendations. A key objective is to distinguish the "sick recovered" from the "healthy recovered." Our hypothesis is that there is a PCS subgroup with autoimmune-mediated systemic and brain-vascular dysregulation, which may lead to circulatory disorders, fatigue, cognitive impairment, depression, and anxiety. This can be clarified using a combination of specific antibody diagnostics and precise clinical, psychological, and apparative testing.

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction. STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines. SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms. SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI. DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses. RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively. LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

AIMS: To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION: Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.

Cerebrovascular events, bleeding complications and device related thrombi in atrial fibrillation patients with chronic kidney disease and left atrial appendage closure with the WATCHMAN™ device.

BACKGROUND: Impaired renal function increases the bleeding risk, leading to a conservative prescription and frequent discontinuation of oral anticoagulation in atrial fibrillation patients with chronic kidney disease (CKD). Interventional left atrial appendage closure (LAAC) might be an alternative therapeutic strategy for these patients. METHODS: We aimed to prospectively assess cerebrovascular (CE) and bleeding events, as well as peri-procedural and long-term complications in a cohort of consecutive patients undergoing interventional LAAC using the WATCHMAN™ device, with focus on CKD patients. RESULTS: One hundred and eighty-nine consecutive patients undergoing interventional LAAC were included in this analysis; 171 (90.5%) patients had a reduced estimated glomerular filtration rate (eGFR; patients for each CKD stage: II = 66; IIIa = 32; IIIb = 43; IV = 18; V = 12). During a follow-up of 310 patient years three (1.0%) patients suffered a CE (two strokes, one transitory ischemic attack) and five (1.6%) other ones a bleeding complication. The observed stroke rate was more than two-thirds and the bleeding risk more than half lower than expected. Device related thrombi (DRT) were detected in twelve (6.5%) patients; women had significantly more DRT than men (12.5% vs. 2.6%; p = 0.009). Patients with an eGFR< 30 ml/min/1.73m2 showed a trend to a higher DRT rate as compared to the opposite group (13.3% vs. 5.1%; p = 0.10). Thrombus resolved with temporary oral anticoagulation therapy in ten patients without sequelae; thrombus consolidation was confirmed by serial TEE controls in the remaining two patients. CONCLUSIONS: Atrial fibrillation patients with CKD have low CE and bleeding rates after LAAC with the WATCHMAN™ device. DRT risk is higher in female and patients with severe CKD. More frequent post-interventional TEE controls might be justified for early DRT detection and safe management of patients at high DRT risk. TRIAL REGISTRATION: (German Clinical Trials Register ID: DRKS00 010768 ; Registration Date 07.07.2016).

Intracardiac echocardiography versus fluoroscopy for endovascular and endocardial catheter navigation during cryo-ablation of the slow pathway in AVNRT patients.

BACKGROUND: A new zero-fluoroscopy technique for electrophysiology catheter navigation relying on intracardiac echocardiography (ICE) has been recently reported (Ice&ICE trial). We investigated potential differences in efficacy, safety or procedural performance between conventional fluoroscopy- and ICE-guided cryothermal ablation (CA) in symptomatic AVNRT patients. METHODS: Clinical and electrophysiological data of AVNRT patients included in the Ice&ICE trial (22 patients, 16 females; =zero-fluoroscopy group) were compared to those of consecutive AVNRT patients, who underwent fluoroscopy-guided CA (25 patients, 17 females; = fluoroscopy group) during the last 2 years in our institution. RESULTS: Slow pathway ablation or modulation was successful in all patients. Fluoroscopy time and radiation dose in the fluoroscopy group were 11.2 ± 9.0 min and 20.3 ± 16.2Gycm2, whereas no fluoroscopy was used in the opposite group (p <  0.001, respectively). EPS duration was not different between the groups (zero-fluoroscopy:101.6 ± 40.2 min, fluoroscopy:99.4 ± 37.2 min, p = n.s.). Catheter placement time was significantly shorter in the fluoroscopy group (2.2 ± 1.6 min vs. 12.0 ± 7.5 min, p <  0.05), whereas cryo-application duration (from the first cryo-mapping to the last CA) was significantly shorter in the zero-fluoroscopy group (27.5 ± 37.0 min vs. 38.1 ± 33.9 min, p <  0.05). Mean cryo-mapping and CA applications were numerically lower in the zero-fluoroscopy group (CM:7.5 ± 5.7 vs. 8.8 ± 6.2; CA:3.1 ± 1.7 vs. 3.2 ± 2.0, p = n.s.). No major adverse events occurred in both groups. After 15.0 ± 4.2 months, arrhythmia recurrence was not different between the groups (4.5% vs. 8.0%, p = n.s.). CONCLUSIONS: Zero-fluoroscopy ICE-guided EP catheter navigation shows comparable efficacy and safety to fluoroscopic guidance during CA in AVNRT patients. ICE visualization of catheters and endocardial structures within the triangle of Koch shortens the cryo-application duration, though time needed for catheter placement is longer, when compared with conventional fluoroscopic guidance, which results in similar mean EPS duration with both navigation techniques. TRIAL REGISTRATION: (German Clinical Trials Register ID: DRKS00011360 ; Registration Date 14.12.2016).

A Secreted Phospholipase A2 Induces Formation of Smooth Muscle Foam Cells Which Transdifferentiate to Macrophage-Like State.

Vascular smooth muscle cells (VSMCs) loaded with lipid droplets (LDs) are markers of atherosclerosis. In this disease, inflammatory Group IIA-secreted phospholipase A2s (GIIA sPLA2s) are highly expressed in VSMCs, but their actions in these cells are unknown. Here, we investigated the ability of myotoxin III (MT-III), an ophidian GIIA sPLA2 sharing structural and functional features with mammalian GIIA sPLA2s, to induce LD formation and lipid metabolism factors involved in this effect. Modulation of VSMC phenotypes by this sPLA2 was also evaluated. Incubation of VSMCs with MT-III significantly increased the number of LDs. MT-III upregulated scavenger receptor type 1 (SR-A1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) protein expression and enhanced acetylated-low density lipoprotein (acLDL) uptake by VSMCs, revealing the ability of a GIIA PLA2 to modulate scavenger receptor activities. MT-III induced translocation and protein expression of PPAR-γ and -ß/δ. Inhibition of peroxisome proliferator-activated receptors (PPARs) and diacylglycerol O-acyltransferase (DGAT) and acyl-CoA:cholesterolacyltransferase (ACAT) enzymes abrogated MT-III-induced LD formation. Moreover, in response to MT-III, VSMCs acquired phagocytic activity and expressed macrophage markers CD68 and MAC-2. In conclusion, MT-III is able to stimulate VSMCs and recruit factors involved in lipid uptake and metabolism, leading to the formation of VSMC-derived foam cells with acquisition of macrophage-like markers and functions.

Zero-fluoroscopy cryothermal ablation of atrioventricular nodal re-entry tachycardia guided by endovascular and endocardial catheter visualization using intracardiac echocardiography (Ice&ICE Trial).

INTRODUCTION: Stochastic damage of the ionizing radiation to both patients and medical staff is a drawback of fluoroscopic guidance during catheter ablation of cardiac arrhythmias. Therefore, emerging zero-fluoroscopy catheter-guidance techniques are of great interest. METHODS AND RESULTS: We investigated, in a prospective pilot study, the feasibility and safety of the cryothermal (CA) slow-pathway ablation in patients with symptomatic atrioventricular-nodal-re-entry-tachycardia (AVNRT) using solely intracardiac echocardiography (ICE) for endovascular and endocardial catheter visualization. Twenty-five consecutive patients (mean age 55.6 ± 12.0 years, 17 female) with ECG-documentation or symptoms suggesting AVNRT underwent an electrophysiology study (EPS) in our laboratory utilizing ICE for catheter navigation. Supraventricular tachycardia was inducible in 23 (92%) patients; AVNRT was confirmed by appropriate stimulation maneuvers in 20 (80%) patients. All EPS in the AVNRT subgroup could be accomplished without need for fluoroscopy, relying solely on ICE-guidance. CA guided by anatomical location and slow-pathway potentials was successful in all patients, median cryo-mappings = 6 (IQR:3-10), median cryo-ablations = 2 (IQR:1-3). Fluoroscopy was used to facilitate the trans-septal puncture and localization of the ablation substrate in the remaining 3 patients (one focal atrial tachycardia and two atrioventricular-re-entry-tachycardias). Mean EPS duration in the AVNRT subgroup was 99.8 ± 39.6 minutes, ICE guided catheter placement 11.9 ± 5.8 minutes, time needed for diagnostic evaluation 27.1 ± 10.8 minutes, and cryo-application duration 26.3 ± 30.8 minutes. CONCLUSIONS: ICE-guided zero-fluoroscopy CA in AVNRT patients is feasible and safe. Real-time visualization of the true endovascular borders and cardiac structures allow for safe catheter navigation during the ICE-guided EPS and might be an alternative to visualization technologies using geometry reconstructions.

Serial Assessment of Natriuretic Peptides in Patients Undergoing Interventional Closure of the Left Atrial Appendage.

BACKGROUND: Closure of the left atrial appendage (LAA) to prevent cardioembolic events is an alternative therapy to oral anticoagulation in patients with non-valvular atrial fibrillation. The LAA is an important source of natriuretic peptides and its exclusion from the circulation may alter the blood level of these hormones, thereby influencing their diagnostic value and clinical effects. METHODS: We aimed to prospectively assess potential changes in mid-regional pro A-type natriuretic peptide (MR-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels 6 weeks and 6 months after interventional LAA closure using the WATCHMAN device. RESULTS: In 29 consecutive patients with successful LAA closure baseline MR-proANP level was 274±208pmol/l and decreased by -24.5±68 (p=0.07) and -15.0±44pmol/l (p=0.10) after 6 weeks and 6 months, respectively. The drop in the MR-proANP level after 6 weeks and 6 months was significant in patients with elevated (≥214pmol/l) baseline MR-proANP level (n=15: -54.3±78.0, p<0.01 and -31.8±45.4pmol/l, p=0.03, respectively) and those with reduced left ventricular ejection fraction (LVEF<45%, n=7: -87.4±97.3, p=0.02 and -60.3±42.6pmol/l, p=0.01, respectively). Baseline NT-proBNP level (median 1054pg/ml; IQR 621-1977pg/ml), sodium, potassium, mean systolic or diastolic blood pressure did not change significantly in the mentioned patient groups. CONCLUSIONS: After LAA closure, MR-proANP level decreased significantly in patients with elevated baseline MR-proANP level or reduced LVEF, whereas NT-proBNP level remained unchanged, thereby altering the correlation coefficient between the two biomarkers. Our findings should be considered when using these biomarkers for diagnostic or prognostic evaluation in patients with interventional LAA closure.

Left atrial enlargement and clinical considerations in patients with or without a residual interatrial shunt after closure of the left atrial appendage with the WATCHMAN™-device.

BACKGROUND: Interventional closure of the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation, high thromboembolic and bleeding risk or bleeding history is an alternative therapeutic strategy to oral anticoagulation. It is not known if the exclusion of the LAA from the blood circulation affects the left atrial volume (LAV) and consequently its prognostic value or the circulatory performance of the heart in humans. METHODS: We aimed to prospectively assess potential changes in baseline LAV, left ventricular ejection fraction (LVEF), NT-proBNP-level and the covered distance in the 6-min walk-test 6 weeks and 6 months after LAA closure with the WATCHMAN™ device. We used serial 3-dimensional transthoracic and transesophageal echocardiography to assess LAV, residual interatrial shunt and device performance in 58 consecutive patients with successful LAA closure. RESULTS: Accurate 3D-echocardiographic data for LAV measurements were evaluable for 51 (91%) patients. Maximum LAV (LAVmax) at baseline was 102.8 ± 30.8 ml and increased significantly to 107.7 ± 32.8 ml after 6 weeks (p < 0.01) and 113.5 ± 34.2 ml after 6 months (p < 0.01). Minimal LAV (LAVmin) increased from 76.9 ± 29.5 ml at baseline to 81.8 ± 30.2 ml after 45 days (p < 0.01) and 82.1 ± 33.3 ml after 6 months (p < 0.01). Similarly, their indexes to BSA (LAVImax and LAVImin) increased significantly, as well. Patients without a residual left-to-right interatrial shunt showed a significantly higher increase in LAVmax or LAVmin. Baseline LVEF, NT-proBNP-level or the distance covered at the 6-min walk test did not significantly change 6 weeks or 6 months after LAA closure. CONCLUSIONS: LAVmax and LAVmin increase significantly after interventional LAA closure. LA enlargement does not correlate with clinical progression of heart failure. Persistent left-to-right interatrial shunt counteracts the LA enlargement. A reduced LA compliance after exclusion of the LAA from the blood circulation with consecutive increase in LA pressure may be a potential cause of LA enlargement and warrants further investigation. TRIAL REGISTRATION: German Clinical Trials Register ID: DRKS00010768 ; Registration Date 07.07.2016.

[Creating Enthusiasm for Surgery - Perceptions of the Impact of Undergraduate Practical Education (Clerkship) for Occupational Choices]. / Für Chirurgie begeistern ­ Einflüsse der Famulatur aus Sicht Studierender auf eine spätere Fachpräferenz.

Background/Aim Surgical and other disciplines have been noticing difficulties in recruiting junior staff for several years. In response to a decrease in interest within study courses, surgical associations recommend better supervision during undergraduate practical education as "clerkships" in order to increase the attractiveness of surgery. This clerkship has an initiation function, as students for the first time - albeit marginally - can act as physicians. The aim of this study was to investigate the impact of clerkships on the disciplinary orientations and preferences of undergraduates' perceptions of specialist training. Methods Medical students of the Otto-von-Guericke University Medical School at Magdeburg were interviewed at 4 different time points in their clinical training (n = 373). The questionnaire included different dimensions on i) their choice of the subjects of clerkships and ii) on their clerkship experiences. Questions were subdivided into 5 basic topics, including 5 options to answer according to "Likert's scale" ranging from 1 to 5 ("completely true" to "does not apply at all"). Data were statistically analysed. Results Clerkships are an important component of medical studies. Undergraduate medical students deliberately use clerkships to get to know and to discriminate between medical disciplines they consider as possible choices for later specialisation. Their own assessment as well as reported experiences of specific clinics, departments or supervisors influence decision-making with regard to medical disciplines and locations/institutions for clerkships. The contents of the clerkships is expected to be closely related to the medical curricula. Students expect a detailed insight and practical, cross-departmental, interdisciplinary integration and collaboration in the medical discipline selected for clerkship. Clerkship experience in surgery affects the students' preference for surgical disciplines. They are a relevant predictor. Conclusion High-quality teaching - an important part of practical undergraduate training (clerkship) is effective in fostering a subsequent surgical orientation. Preference for surgical specialisation can be strengthened during medical studies by preparing seminars and extended practical experiences during clerkship.

Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.

Ephrin-A1/EphA4-mediated adhesion of monocytes to endothelial cells.

The Eph receptors represent the largest family of receptor tyrosine kinases. Both Eph receptors and their ephrin ligands are cell-surface proteins, and they typically mediate cell-to-cell communication by interacting at sites of intercellular contact. The major aim of the present study was to investigate the involvement of EphA4-ephrin-A1 interaction in monocyte adhesion to endothelial cells, as this process is a crucial step during the initiation and progression of the atherosclerotic plaque. Immunohistochemical analysis of human atherosclerotic plaques revealed expression of EphA4 receptor and ephrin-A1 ligand in major cell types within the plaque. Short-time stimulation of endothelial cells with the soluble ligand ephrin-A1 leads to a fourfold increase in adhesion of human monocytes to endothelial cells. In addition, ephrin-A1 further increases monocyte adhesion to already inflamed endothelial cells. EphrinA1 mediates its effect on monocyte adhesion via the activated receptor EphA4. This ephrinA1/EphA4 induced process involves the activation of the Rho signaling pathway and does not require active transcription. Rho activation downstream of EphA4 leads to increased polymerization of actin filaments in endothelial cells. This process was shown to be crucial for the proadhesive effect of ephrin-A1. The results of the present study show that ephrin-A1-induced EphA4 forward signaling promotes monocyte adhesion to endothelial cells via activation of RhoA and subsequent stress-fiber formation by a non-transcriptional mechanism.

[Cardiovascular prevention in Saxony-Anhalt : Necessity and new perspectives]. / Kardiovaskuläre Prävention in Sachsen-Anhalt : Notwendigkeit und neue Perspektiven.

Cardiovascular risk factors (high blood pressure, smoking, overweight, type 2 diabetes, dyslipidemia, physical inactivity) substantially rise with increasing age, particularly after middle age, whereby women are affected to a much greater extent. In the population of Saxony-Anhalt the prevalence of cardiovascular risk factors is clearly increased and the population structure in Saxony-Anhalt is particularly characterized by a high average age as well as high morbidity and mortality rates due to cardiovascular diseases. Saxony-Anhalt therefore provides a model character for the demographic development in Europe. This review article discusses strategies for the implementation of target group-specific cardiovascular preventive strategies in the Federal State of Saxony-Anhalt with special consideration of age and sex. When preventive medicine facilities are established and innovative treatment possibilities for patients with cardiovascular risks are created, prevention should also become available in rural areas.

DiADEM-Dance against Dementia-Effect of a Six-Month Dance Intervention on Physical Fitness in Older Adults with Mild Cognitive Impairment: A Randomized, Controlled Trial.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial, 55 patients with MCI were randomized into a sportive dance training (IG; n = 26; age: 70.7 ± 5.6 years; 62% female) or an inactive control group (CG; n = 24; age: 69.1 ± 6.8 years; 46% female). The dance group received two 90 min dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heart rate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength, and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength, although these were not statistically significant. HRV displayed a non-significant decrease following the intervention. Conclusions: The results of this randomized controlled trial suggest that sportive dance training can preserve elements of physical fitness (i.e., cardiorespiratory fitness) in older adults with MCI. Although improvements in the other parameters (i.e., leg and handgrip strength) were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence. For future studies, we recommend a longer training duration paired with precise control of regular physical activity levels, an important confounding factor.