Search

Pericytes are mural cells that play an important role in regulation of angiogenesis and endothelial function. Cadherins are a superfamily of adhesion molecules mediating Ca2+-dependent homophilic cell-cell interactions that control morphogenesis and tissue remodeling. To date, classical N-cadherin is the only cadherin described on pericytes. Here, we demonstrate that pericytes also express T-cadherin (H-cadherin, CDH13), an atypical glycosyl-phosphatidylinositol (GPI)-anchored member of the superfamily that has previously been implicated in regulation of neurite guidance, endothelial angiogenic behavior, and smooth muscle cell differentiation and progression of cardiovascular disease. The aim of the study was to investigate T-cadherin function in pericytes. Expression of T-cadherin in pericytes from different tissues was performed by immunofluorescence analysis. Using lentivirus-mediated gain-of-function and loss-of-function in cultured human pericytes, we demonstrate that T-cadherin regulates pericyte proliferation, migration, invasion, and interactions with endothelial cells during angiogenesis in vitro and in vivo. T-cadherin effects are associated with the reorganization of the cytoskeleton, modulation of cyclin D1, α-smooth muscle actin (αSMA), integrin β3, metalloprotease MMP1, and collagen expression levels, and involve Akt/GSK3β and ROCK intracellular signaling pathways. We also report the development of a novel multiwell 3-D microchannel slide for easy analysis of sprouting angiogenesis from a bioengineered microvessel in vitro. In conclusion, our data identify T-cadherin as a novel regulator of pericyte function and support that it is required for pericyte proliferation and invasion during active phase of angiogenesis, while T-cadherin loss shifts pericytes toward the myofibroblast state rendering them unable to control endothelial angiogenic behavior.

Extracellular vesicles (EVs) are considered as valuable biomarkers to discriminate healthy from diseased cells such as cancer. Passing cytosolic and plasma membranes before their release, EVs inherit the biochemical properties of the cell. Here, we determine protein profiles of single EVs to understand how much they represent their cell of origin. We use a microfluidic platform which allows to immobilize EVs from completely isolated single cells, reducing heterogeneity of EVs as strongly seen in cell populations. After immunostaining, we employ four-color total internal reflection fluorescence microscopy to enumerate EVs and determine their biochemical fingerprint encoded in membranous or cytosolic proteins. Analyzing single cells derived from pleural effusions of two different human adenocarcinoma as well as from human embryonic kidney (SkBr3, MCF-7 and HEK293, respectively), we observed that a single cell secretes enough EVs to extract the respective tissue fingerprint. We show that overexpressed integral plasma membrane proteins are also found in EV membranes, which together with populations of colocalized proteins, provide a cell-specific, characteristic pattern. Our method highlights the potential of EVs as a diagnostic marker and can be directly employed for fundamental studies of EV biogenesis., Analytical Chemistry, 95 (3), ISSN:1520-6882, ISSN:0003-2700

Zusammenfassung Hintergrund Die Transfusion von Erythrozytenkonzentraten (EK) ist mit verschiedenen Nebenwirkungen assoziiert, die u. a. durch Lagerungsschäden an Erythrozyten hervorgerufen werden. Die Zellen verändern ihre Struktur und setzen dabei Kalium sowie Lactat frei. Zur Minimierung dieser negativen Effekte können die Erythrozyten mithilfe einer maschinellen Autotransfusion (MAT) unter Verwendung von Waschlösungen aufgereinigt werden. Ziel der Arbeit Untersuchung der Auswirkungen zweier Waschlösungen auf die gelagerten Erythrozyten. Material und Methode In der vorliegenden Studie wurden 30 EK mittels MAT (Xtra, LivaNova, München, Deutschland) gewaschen. Der Goldstandard 0,9 %ige Kochsalzlösung (n = 15; N‑Gruppe) wurde mit einer 4 mmol/l kaliumhaltigen Hämofiltrationslösung (HF) (n = 15; HF-Gruppe; Duosol) verglichen. In einer Subgruppenanalyse wurde eine Differenzierung bezogen auf die Lagerdauer der EK (7, 14, 37 Tage) bis zur Durchführung der MAT vorgenommen. Untersucht wurde der Einfluss der Waschlösungen sowie des EK-Alters auf ATP, Lactat, Glucose, Elektrolyte und Zitrat zu drei Messzeitpunkten vor MAT (EKprä), unmittelbar danach (EKpost) und nach 10 h im Retransfusionsbeutel (EKpost10h). Ergebnisse und Diskussion Die ATP-Konzentration nimmt durch die MAT-Waschung von EKprä zu EKpost signifikant zu (n = 30). Bei 37 Tage alten EK nimmt die ATP-Konzentration in der HF-Gruppe nach MAT stärker zu als in der N‑Gruppe. Durch die MAT-Waschung werden die Kalium‑, Lactat‑, Glucose- und Zitratkonzentration signifikant reduziert. Die MAT-Behandlung gelagerter EK verbessert deren Qualität. Das Waschen mit einer HF-Lösung führt zu einer physiologischeren Elektrolytzusammensetzung. Selbst 10 h nach MAT mit einer HF-Lösung ist die Qualität eines 37 Tage alten EK bezüglich der untersuchten Parameter mit einem jungen 7 Tage gelagerten, nichtgewaschenen EK vergleichbar.

Funding Acknowledgements Type of funding sources: None. Background Preprocedural transesophageal echocardiography (TEE) screening for LA or LAA thrombi is standard operating procedure (SOP) in most centers performing atrial fibrillation ablation. However, TEE is a procedure that imposes procedural risks for patients and is often challenging to include in daily clinical practice, besides causing patient discomfort. At our center, we have implemented a novel SOP regarding preprocedural TEE screening for atrial thrombi. Patients who present in sinus rhythm and suffer from a low stroke risk based on CHADS-VASC-Score ( Purpose The purposes of this study are to assess whether a novel SOP regarding preprocedural TEE screening for LA thrombi can effectively reduce the number of TEEs performed without imposing patients to a higher risk for strokes in course of catheter ablation of atrial arrhythmias. Methods Data of 2335 consecutive patients who received catheter ablation of atrial arrhythmias at the University Hospital of Cologne between 2018 and 2022 was retrospectively analyzed. All patients treated until March 2020 received preprocedural TEE before every ablation procedure, screening for atrial thrombi. In all following cases, a novel SOP was applied: Patients in sinus rhythm at the beginning of the procedure who were either sufficiently anticoagulated or had a CHADS-VASC-Score Results Out of 2335 included patients, 961 (41%) were treated according to the old SOP and 1374 (59%) patients were treated according to the new SOP. Both groups did not differ significantly regarding their baseline parameters. Performed ablation procedures (old SOP vs. new SOP) consisted of PVI (689, 68.8% vs. 921, 64.5%; p=0.04), re-PVI (179, 17.8% vs. 240, 16.8%; p=0.52), substrate-based ablation of persistent AF (70, 7% vs. 186, 13%; p Conclusion We demonstrate outcomes of a novel SOP for pre-procedural TEE screening of LA thrombi that limits TEEs to patients who are at high risk of stroke according to current guidelines and CHADS-VASC-Score. Patients who present in sinus rhythm and have a CHADS-VASC-Score

Funding Acknowledgements Type of funding sources: None. Background The newly introduced non-thermal pulsed field ablation (PFA) is a promising technology to achieve fast pulmonary vein isolation (PVI) with high acute success rates and comparable safety features. However, previous studies have shown that high power short duration ablation (HPSD) is also highly effective and fast to achieve PVI with potentially less AF recurrence. Data comparing PFA to HPSD-PVI is lacking. Objective This study compared procedural parameter and outcome using the novel PFA-PVI to HPSD-PVI in patients with paroxysmal or persistent atrial fibrillation (PAF/persAF). Methods Between 09/2021 and 10/2022 all consecutive patients undergoing de-novo PVI (PFA or HPSD) were included in this analysis. For PFA-PVI a shapeable (flower/basket shape) 5 spline 20 electrode catheter was used. For HPSD-PVI a power setting of 70W/7s (70W/5s at posterior wall) was considered as HPSD. Furthermore, a 3D mapping system was used. Follow-up consisted of out-clinic pts visit, teleconsultation, 48h Holter ECG and CIED interrogation if applicable. Results A total of 114 patients (57 PFA [17(30%) PAF; 40(70%) persAF 40(70%)] were included in this analysis. PVI was successful in all patients. The PFA group revealed a significantly shorter procedure duration (65±17 min vs. 95±23 min, p At follow-up after three months (33±12 days) 46 PFA (80.7%) and 44 HPSD pts (77.2%) were free from atrial arrhythmia after a single procedure (p=0.819). One clinically non.significant PV stenosis occurred in the HPSD group. Conclusion PFA and HPSD-PVI seem to be highly effective and safe to achieve PVI in the setting of PAF and persAF with comparable arrhythmia free survival. However, procedure duration for PFA PVI is significantly shorter and therefore may be of potential benefit.

Funding Acknowledgements Type of funding sources: None. Background Pulmonary vein isolation (PVI) using cryoballoon (CB) ablation has comparable efficacy and safety compared to radiofrequency ablation (RFA) for first procedure treatment of symptomatic atrial fibrillation (AF). Redo procedures are usually done with RFA, allowing for selective pulmonary vein re-isolation as well as formation of additional lesion sets. It is unclear whether a combination of different ablation methods in the index procedure and the redo procedure provides an efficacy benefit compared to the use of RFA in both procedures. Purpose We aimed to compare the efficacy and procedural characteristics of redo AF-ablation-procedures in terms of the technology used in the first ablation procedure (Cryo vs. RFA). Methods We performed a retrospective analysis of our internal AF ablation registry, containing 310 consecutive patients that underwent a second ablation procedure for recurrence of symptomatic AF from November 2019 to August 2022. For 36 patients the method in the first procedure was unknown or a method alternative to RFA or Cryo was used, leaving 274 patients for analysis. Patients were stratified into two groups, based on the technology used in the index procedure (Cryo vs. RFA). Patients underwent follow-up at 3 and 12 months (at 12 months blanking phase recurrences were excluded), either as part of a prescheduled visit or via telephone call to the primary care provider or to the patient. Results 139 patients underwent the index PVI using RFA vs. 135 patients in which the index procedure was performed with Cryo. Baseline characteristics including sex (37.4% vs. 48.9% female, p=0.055), mean age (68.9 ± 9.7 vs. 68.7 ± 10.9 years, p=0.915), BMI (26,8 ± 4.1 vs. 28.4 ± 4.3 kg/m2. p=0.345), percentage of patients with paroxysmal AF (38.9% vs. 32.6%, p=0.280), arterial hypertension (69.6% vs. 67.4%, p=0.762), beta blocker use (84.1% vs. 80.7% p=0.472), class Ic or III antiarrhythmic drug use on discharge (40.3% vs. 45.9%, p=0.346) and mean left atrial diameter (39.7 ± 5.7 mm vs. 39.9± 5.6 mm. p=0.731) were all similar between groups. In the redo procedures, pulmonary vein reisolation was performed in 85.2% vs. 78.6% (p=0.204) after RFA vs. after Cryo. Additional substrate modifications including lines and defragmentation of low voltage potentials were done in 26.6% vs. 34.1% patients (p=0.179). Procedural duration (147.2 (110-180) vs. 139.0 (100-160) min, p=0.501), fluoroscopy time (12.1 (8.2-17.0) vs. 13.1 (8.2-19.0), p=0,638), and fluoroscopy dose (2525 (1425-3935)vs. 2544 (1356-4840) mGycm2, p=0.806) were comparable between groups. The rates of AF recurrence at 3 month follow-up (27.0% vs. 26.4%, p=0.924) and 12 month follow-up (25.6 vs. 34.5%, p=0.257) were similar between groups. Conclusion In this single center retrospective analysis, there was no difference in efficacy and procedural characteristics of redo AF-ablation-procedures based on the ablation method used in the index procedure.

Funding Acknowledgements Type of funding sources: None. Background Pace mapping is an established technique to localize the origin of premature ventricular contractions (PVC). The QRS morphology induced by endocardial pacing is compared with a previously recorded template of the target arrhythmia. Based upon historic in-vitro models pacing at the arrhythmia’s coupling interval (CI) and stimulation threshold has become the gold standard in pace mapping. Purpose There is a paucity of data supporting pacing at the CI and stimulation threshold as the gold standard for pace mapping. In this prospective study, we sought to assess systematically the impact of variations of pacing output and cycle length on the resulting QRS morphology during pace mapping in the context of PVC ablation. Methods All patients undergoing ablation of idiopathic PVC were prospectively enrolled in this study. Pace mapping was performed using four different parameter settings: (1) A predefined fixed burst at maximum output (10V/2ms), (2) fixed burst at stimulation threshold, (3) coupling interval at maximum output and (4) coupling interval at stimulation threshold. Pacing cycle length (PCL) of the fixed burst was defined as follows: For a CI≤450ms = PCL of CI+100ms and for a CI≥450 = PCL of CI-100ms. Using an automated waveform comparison algorithm (Bard® LabSystem™ PRO software; Boston Scientific, MA, USA), the resulting QRS complexes were matched with the clinical PVC, and with the gold standard. For every parameter setting the mean of the matching percentage of three QRS complexes entered the analysis. Results We report data of the first 47 consecutive patients (57±18 years, 64% male) enrolled in this ongoing study between May 2021 and September 2022. The pacing protocols were performed at 75 different sites: 6/75 epicardially via great cardiac vein, 38/75 in the RVOT, 23/75 in LVOT and 8/75 in the left ventricular cavity. When comparing the QRS morphologies resulting from the four different pace mapping settings with the clinical PVC, the univariate analysis revealed no difference between groups (p=0.9). Furthermore, there was no difference comparing the paced QRS morphologies at different output and cycle length to the gold standard of threshold pacing at coupling interval (p=0.9). Conclusion Variations of pacing output and stimulation cycle length during pace mapping does not affect QRS morphology during PVC ablation. Applying a modern automated waveform comparison tool, no advantage was observed when comparing with the gold standard. It is therefore reasonable to assume, that pace mapping can be performed using an easily applicable setting of a fixed burst at maximum pacing output.

Funding Acknowledgements Type of funding sources: None. Background Mapping, using the novel omnipolar technology (OT) obtains omnipolar signals displaying true voltage, real-time wavefront direction and speed, independent of catheter orientation and external reference. Employment of OT potentially overcomes so called "bipolar blindness" (conventional bipolar electroanatomic mapping). Hence, OT potentially improves substrate assessment, comprehension of tachycardia mechanisms and gap detection after previous catheter ablation (CA). Purpose Purposes of our study was to analyze previously performed left atrial (LA) and left ventricular (LV) maps for differences using automated OT vs. SD vs. the previously published HD Wave (HDW) algorithm. Methods Maps of patients undergoing CA for atrial or ventricular arrhythmia were initially acquired using HDW settings in conjunction with the Advisor HD Grid mapping catheter. These maps were then analyzed retrospectively applying the automated OT algorithm vs. SD vs. HDW. to reveal differences in voltage and point density. Additionally, detection of pulmonary vein (PV) gaps and LV scar area was evaluated. Results In 45 consecutive patients 135 maps were analyzed. The study population undergoing CA consisted of: 30 (22.2%) patients undergoing repeated CA for recurrence of persistent atrial fibrillation (persAF)/left atrial tachycardia (AT) and 15 (11.1%) patients with ventricular tachycardia (VT) or premature ventricular contractions (PVC). Atrial maps revealed a significantly higher point density using OT (21471) vs. SD (6682) or HDW (12189, p Conclusion Using OT results in a higher voltage and point density compared to SD and HDW. Therefore displayed scar extend is significantly smaller in atrial and ventricular maps. Also, more PV gaps were detected using OT. The OT algorithm potentially improves scar delineation, facilitates substrate characterization, and may improve procedural outcome.

Funding Acknowledgements Type of funding sources: None. Background Pulmonary vein isolation (PVI) using cryoballoon (CB) catheter ablation has emerged as a cornerstone for treatment of atrial fibrillation (AF). Recently pulsed field ablation (PFA) has been introduced for PVI. First data show high acute and favorable long-term outcome. So far, data comparing these "single shot" devices is sparse. Objective This analysis sought to provide procedural and outcome data comparing PFA to CB PVI. Furthermore, potentially postprocedural discomfort was evaluated. Methods A retrospective analysis of PVI procedures using PFA or CB was performed. Discomfort analysis was obtained by prescribed analgesic medication within first 48 h after PVI (fully digital patient file). During follow-up (FU) repeat outpatient visits and Holter ECG were performed. Results In all 108 patients with AF (54 PFA and 54 CB; PFA: 37 (69 %) men; CB: 38 (70 %) men) successful PVI was achieved. There were no significant differences regarding baseline characteristics. 17 (31 %) patients in the PFA group and 18 (33 %) patients in the CB group had paroxysmal AF. Procedure time trended to be shorter in the PFA group (PFA: 64.5±17.5 minutes; CB: 73.0±24.8 minutes; p=0.07). Sub-analysis of the PFA group revealed a significant shortening of procedure duration over time (first 27 PFA vs. second 27 PFA: 72.9±19.1 minutes vs. 56.1±10.7 minutes, p=0.001). Significantly less contrast medium was used for PFA PVI as compared to CB PVI (PFA: 12± 6 ml; CB: 51± 29 ml, p Conclusion A comparison of PFA to CB PVI revealed a comparable efficacy and safety profile with a steep learning curve and potentially shorter procedure duration. Amount of contrast medium is significantly higher for CB PVI. So far, arrhythmia-free survival seems to be still equal between both techniques. However, PFA is a safe and effective alternative to CB for PVI.

Funding Acknowledgements Type of funding sources: None. Background Pulmonary vein isolation (PVI) is an established therapy for symptomatic atrial fibrillation (AF) and the cryoballoon (CB) has become a standard tool for PVI. But the technology is limited in certain ways. The novel multi-electrode balloon catheter promises the advantages of a balloon technology in combination with 3D-mapping and more flexible energy delivery. Purpose There is very limited data available regarding the safety and efficacy of the Heliostar™ RF-balloon. We therefore aimed to assess procedure characteristics, efficacy, and safety in direct comparison with the established CB. Methods All patients undergoing PVI using the Heliostar™ between September 2021 and March 2022 were included in this single center registry. Procedural data and outcome were assessed and compared with data from consecutive patients undergoing initial PVI for paroxysmal AF with the CB from our specifically designed database. Results A total of 251 consecutive patients (63±13 years, 54% male) were included. Of those 28 patients undergoing RF-balloon and 223 patients CB PVI. Baseline parameters did not differ between groups. Acute PVI was achieved in all patients using CB and in 26/28 patients (93%) with the RF-balloon. In 2/28 patients an additional single tip catheter was needed. A mean of 11.2±4.9 RF-applications with 2.8±1.4 applications per vein (LSPV 3.2±2.9, LIPV 2.6±2.5, RSPV 2.8±2.0 and RIPV 1.8±0.8) were necessary to achieve a durable isolation. Using the CB, significantly less applications (5.9±2.2;p= Conclusion The novel multi-electrode RF-balloon has shown to be safe and effective with good long-term results. In comparison with the CB, time to isolation was significantly shorter but procedure durations were longer and fluoroscopy exposition was higher using the first generation Heliostar™ without LassostarNav®. This can be attributed to the learning curve applying a new ablation system and the necessity for separate 3D map preparation. More experience is needed in the future, especially with the new generation Heliostar™ to determine the real benefits.

Cells have a phenotypic heterogeneity even in isogeneic populations. Differences in secretion of substances have been well-investigated with single mammalian cells. However, studies on the heterogeneity of secreted substances at the single-bacterial-cell level are challenging due to the small size, motility, and rapid proliferation of bacterial cells such asEscherichia coli. Here, we propose a microfluidic device to achieve an isolated culture of single bacterial cells and capture of extracellular vesicles (EVs) secreted from individuals. The device has winding channels to trap single rod-shapedE. colicells at their entrances. Isolated single mother cells grew constantly up to 24 h, while their daughter cells were removed by flow. The flow carried EVs of the trapped cells along the channel, whose surface was rendered positively charged to electrostatically capture negatively charged EVs, followed by staining with a lipophilic dye to detect EVs by microscopy. Our results underline that the amounts of segregated EVs vary among cells. Moreover, individual responses to perturbation using a membrane-perturbing antibiotic were observed in growth dynamics and EV secretion of living-alone bacteria. The proposed method can be applied to detect other secreted substances of interest, possibly paving the way for elucidating unknown heterogeneities in bacteria.

Immunoassays are frequently used for analysis of protein biomarkers. The specificity of antibodies enables parallel analysis of several target proteins, at the same time. However, the implementation of such multiplexed assays into cost-efficient and mass-producible thermoplastic microfluidic platforms remains difficult due to the lack of suitable immobilization strategies for different capture antibodies. Here, we introduce and characterize a method to functionalize the surfaces of microfluidic devices manufactured in the thermoplastic material cyclic olefin copolymer (COC) by a rapid prototyping process. A laser-induced immobilization process enables the surface patterning of anchor biomolecules at a spatial resolution of 5 mu m. We employ the method for the analysis of prostate cancer associated biomarkers by competitive immunoassays in a microchannel with a total volume of 320 nL, and successfully detected the proteins PSA, CRP, CEA and IGF-1 at clinically relevant concentrations. Finally, we also demonstrate the simultaneous analysis of three markers spiked into undiluted human plasma. In conclusion, this method opens the way to transfer multiplexed immunoassays into mass-producible microfluidic platforms that are suitable for point of care applications., Lab on a Chip, 23 (3), ISSN:1473-0197, ISSN:1473-0189

High numbers of tumour-associated macrophages (TAMs) in the tumour microenvironment are associated with a poor prognosis. However, the effect of TAMs on tumour progression depends on the proteins secreted by individual TAMs. Here, we developed a microfluidic platform to quantitatively measure the secreted proteins of individual macrophages as well as macrophages polarized by the culture medium derived from breast cancer cells. The macrophages were captured in hydrodynamic traps and isolated with pneumatically activated valves for single-cell analysis. Barcoded and functionalized magnetic beads were captured in specially designed traps to determine the secreted proteins by immunoassay. Individual bead trapping facilitated the recording of the protein concentration since all beads were geometrically constrained in the same focal plane, which is an important requirement for rapid and automated image analysis. By determining three signaling proteins, namely interleuking 10 (IL-10), vascular endothelial growth factor (VEGF), and tumour necrosis factor alpha (TNF-alpha), we successfully distinguished between differently polarized macrophages. The results indicate a heterogeneous pattern, with M2 macrophages characterized by a higher secretion of IL-10, while M1 macrophages secrete high levels of the inflammatory cytokine TNF-alpha. The macrophages treated with the supernatant from cancer cells show a similar signalling pattern to M2 macrophages with an increased secretion of the pro-tumoural cytokine VEGF. This microfluidic method resolves correlations in signaling protein expression at the single-cell level. Ultimately, single-macrophage analysis can contribute to the development of novel therapies aimed at reversing M2-like TAMs into M1-like TAMs., Lab on a Chip, 23 (2), ISSN:1473-0197, ISSN:1473-0189

Evolution is essential to the generation of complexity and ultimately life. It relies on the propagation of the properties, traits, and characteristics that allow an organism to survive in a challenging environment. It is evolution that shaped our world over about four billion years by slow and iterative adaptation. While natural evolution based on selection is slow and gradual, directed evolution allows the fast and streamlined optimization of a phenotype under selective conditions. The potential of directed evolution for the discovery and optimization of enzymes is mostly limited by the throughput of the tools and methods available for screening. Over the past twenty years, versatile tools based on droplet microfluidics have been developed to address the need for higher throughput. In this Review, we provide a chronological overview of the intertwined development of microfluidics droplet-based compartmentalization methods and in vivo directed evolution of enzymes., Angewandte Chemie. International Edition, 60 (46), ISSN:1433-7851, ISSN:1521-3773, ISSN:0570-0833

Microfluidic tools are well suited for studying bacteria as they enable the analysis of small colonies or single cells. However, current techniques for studying bacterial response to antibiotics are largely limited to static dosing. Here, we describe a microfluidic device and a method for entrapping and cultivating bacteria in hydrogel plugs. Ring-shaped isolation valves are used to define the shape of the plugs and also to control exposure of the plugs to the surrounding medium. We demonstrate bacterial cultivation, determination of the minimum inhibitory concentration of an antibiotic, and transient dosing of an antibiotic at sub-1-h doses. The transient dosing experiments reveal that at dose durations on the order of minutes, ampicillin's bactericidal effect has both a time and concentration dependency. Published under an exclusive license by AIP Publishing., Biomicrofluidics, 16 (4), ISSN:1932-1058

Zusammenfassung Hintergrund Trotz multipler Therapieoptionen ist heutzutage eine Heilung der juvenilen rezidivierenden respiratorischen Larynxpapillomatose (JORRP, „juvenile onset recurrent respiratory laryngeal papillomatosis“) nicht möglich. Außerdem weisen viele Medikamente nicht zu unterschätzende Nebenwirkungen auf. Fragestellung Darstellung aktueller und früherer Therapieoptionen der JORRP mit Diskussion von Wirkstoff, Darreichungsart und Dosierungen. Materialien und Methoden Literaturrecherche und -zusammenfassung. Analyse der Therapieoptionen anhand von Wirkstoff, Darreichungsart, Dosierungen und Nebenwirkungen. Ergebnisse Die chirurgische Therapie bleibt weiterhin Grundlage der Therapie. Multiple Therapieoptionen werden beschrieben, jedoch keine mit der Aussicht auf eine vollständige Remission. Der Funktionserhalt der Stimme sowie die Verlängerung des Zeitintervalls zwischen den Eingriffen bzw. die Verminderung der Papillommasse im Rezidivfall bleiben oberstes Gebot. Neue immunmodulatorische Therapieoptionen werden aktuell näher untersucht. Schlussfolgerungen Einige der mannigfaltigen Therapieoptionen scheinen zwar vielversprechend zu sein und ein sicheres Nebenwirkungsprofil aufzuweisen, jedoch reicht die aktuelle Datenlage, die überwiegend auf Fallserien basiert, nicht für eine generelle Therapieempfehlung aus. Weitere prospektive Studien mit einer größeren Patientenzahl sind nötig.

Funding Acknowledgements Type of funding sources: None. Background Pace mapping is an established technique to localize the origin of premature ventricular contractions (PVC). The QRS morphology induced by endocardial pacing is compared with a previously recorded template of the target arrhythmia. Based upon historic in-vitro models pacing at the arrhythmia’s coupling interval (CI) and stimulation threshold has become the gold standard in pace mapping. Purpose There is a paucity of data supporting pacing at the CI and stimulation threshold as the gold standard for pace mapping. In this prospective study, we sought to assess systematically the impact of variations of pacing output and cycle length on the resulting QRS morphology during pace mapping in the context of PVC ablation (NCT05061498). Methods All patients undergoing ablation of idiopathic PVC were prospectively enrolled in this study. Pace mapping was performed using four different parameter settings: (1) A predefined fixed burst at maximum output (10V/2ms), (2) fixed burst at stimulation threshold, (3) coupling interval at maximum output and (4) coupling interval at stimulation threshold. Pacing cycle length (PCL) of the fixed burst was defined as follows: for a CI ≤450ms = PCL of CI+100ms and for a CI ≥450 = PCL of CI-100ms. Using an automated waveform comparison algorithm, the resulting QRS complexes were matched with the clinical PVC, and with the gold standard. For every parameter setting the mean of the matching percentage of three QRS complexes entered the analysis. Results We report data of the first 22 consecutive patients (53±15 years, 64% female) enrolled in this ongoing study between May and November 2021. The pacing protocols were performed at 39 different sites: 5/39 epicardially via great cardiac vein, 15/39 in the RVOT 12/39 and 7/22 in the left ventricular cavity. When comparing the QRS morphologies resulting from the four different pace mapping settings with the clinical PVC, the univariate analysis revealed no difference between groups (p=0.9). Furthermore, there was no difference comparing the paced QRS morphologies at different output and cycle length to the gold standard of threshold pacing at coupling interval (p=0.9). Conclusion Variations of pacing output and stimulation cycle length during pace mapping does not affect QRS morphology during PVC ablation. Applying a modern automated waveform comparison tool, no advantage was observed when comparing with the gold standard. It is therefore reasonable to assume, that pace mapping can be performed using an easily applicable setting of a fixed burst at maximum pacing output.

Funding Acknowledgements Type of funding sources: None. Background Pulmonary vein isolation (PVI) is an established therapy for symptomatic atrial fibrillation (AF). Traditional point by point ablation can be time consuming requiring advanced training. Novel radiofrequency (RF) ablation techniques sought to facilitate PVI. Point by point ablation using high power short duration (HPSD) settings has already shown to be safe and effective whereas there is paucity of data using a novel multi-electrode balloon catheter (Heliostar™, Biosense Webster, CA, USA). Purpose We aimed to assess procedure characteristics, efficacy, and safety of the Heliostar™ RF-balloon catheter in direct comparison with the latest RF ablation technique. Methods All patients undergoing PVI using the Heliostar™ between September and November 2021 were included in this ongoing single center registry. Procedural data and outcome were assessed and compared with data from patients undergoing initial PVI for paroxysmal AF with the HPSD approach from our specifically designed database. A power setting of 70W/7s (70W/5s at posterior wall) was considered as HPSD. Results A total of 51 consecutive patients (61±16 years, 49% male) were included. Of those 13 patients undergoing RF-balloon and 38 patients HPSD ablation. Baseline parameters did not differ between groups. Acute PVI was achieved in all patients. For every RF-application with the RF-balloon all necessary criteria were met: Inflation index was between 0.9 and 1.0 and a minimum of 9/10 electrodes were within impedance range. A mean of 2.8±1.4 applications per vein (LSPV 3.2±2.9, LIPV 2.6±2.5, RSPV 2.8±2.0 and RIPV 1.8±0.8) were necessary to achieve durable isolation. The mean maximum esophageal temperature was 40.2±0.8°C. When comparing procedural parameters with HPSD no statistically significant difference was seen regarding procedure duration (Heliostar™ 111±28min and HPSD 100±25min; p=0.3) and left atrial dwell time (Heliostar™ 90±23min and HPSD 80±26min; p=0.08). Fluoroscopy time (Heliostar™ 17±4min and HPSD 13±5min; p=0.005) and dose (Heliostar™ 3961±1325mGy*cm2 vs. HPSD 3153±1833mGy*cm2; p=0.04) were higher in the Heliostar™ group. No major complication occurred in both groups. A three month follow up was available for 10 patients in the Heliostar™ and for 38 patients in the HPSD group. All 10 Heliostar™ patients and 79% of the HPSD patients were free from atrial arrhythmias at follow up. Conclusion The novel multi-electrode RF-balloon has shown to be safe and effective in the first clinical routine AF ablation procedures. The tendency towards longer LA dwell times, procedure durations and the significantly higher fluoroscopy exposition in comparison with the HPSD PVI can be attributed to the learning curve applying a new ablation system. More experience is needed in the future to determine the benefits of the novel RF-balloon.

Funding Acknowledgements Type of funding sources: None. Background Cryoballoon-(CB)- and radiofrequency-(RF)-ablation are the most common techniques for pulmonary vein isolation (PVI) in patients (pts) with symptomatic atrial fibrillation (AF). An increasing number of pts undergoing PVI are obese. Objective To address the paucity of procedural differences and outcome data of CB- vs. RF-based PVI in relation to body mass index (BMI) of AF patients. Methods All pts undergoing de novo PVI between 01/2018-08/2019 at our university hospital were included in this retrospective analysis. Pts of each group (CB-PVI vs. RF-PVI) were subdivided based on their BMI: normal weight BMI Results A total of 526 pts (62% male, 65.3±11.2 years) underwent successful de novo PVI (320 CB and 206 RF). Especially in obese patients, differences in procedural characteristics were noted: A significantly increased contrast medium volume in CB group (all: CB 50 [40-80] vs. RF 20 [20-30], p A 12-month follow up was available in 480 of 526 (91%) pts. Freedom from any arrhythmia was comparable between CB-PVI and RF-PVI (CB 77% vs. RF 75%, p=0.63). However, for obese pts a trend towards higher AF recurrence rate after RF- compared to CB-PVI was observed (BMI≥35: CB 24% vs. RF 50%, p=0.099). Conclusion For obese pts CB-PVI is similarly safe and effective as RF-PVI. The significantly shorter procedure time for CB-PVI may minimize potential obesity-related complications. However, the lower contrast medium quantity and fluoroscopy dose in RF-PVI must be considered. AF recurrence rates were comparable between CB-PVI und RF-PVI. Randomised trials are needed to evaluate the long-term freedom of AF recurrence in pts with higher BMI comparing CB- vs. RF-based PVI and possible obesity related complication.

Funding Acknowledgements Type of funding sources: None. Background Several predictive scores for atrial fibrillation (AF) recurrence after ablation have been developed, only some of these are validated in prospective cohorts. The predictive value of such scores has thus far been limited, and many have not been compared with one another. Aims We sought to compare the predictive value of seven previously described risk scores ((CHA2DS2 and CHA2DS2-VASC, HATCH, APPLE, CAAP-AF, BASE-AF2, MB-LATER) for prediction of AF recurrence risk at 12 months after AF ablation. Further, we aimed to identify additional variables to predict recurrences after AF ablation. Methods We analyzed data from of our prospective digital AF ablation registry to compare the previously published scores in an independent and prospective cohort (n=883, 50.8% with paroxysmal AF). Patients were undergoing de-novo ablation of AF received a pulmonary vein isolation (PVI) using radiofrequency (RF) ablation or cryoablation. Ablation procedures for recurrences of AF after initial PVI included re-isolation of the pulmonary veins by RF ablation, with additional substrate modification at the operators’ discretion. Early recurrence and recurrence after ablation were defined as any AF or atrial tachycardia episode lasting ≥ 30 s in the first 3 months after ablation and from the end of the 3-month period to 12 months after ablation. Follow-up of patients was scheduled at regular intervals 3 and 12 months after ablation, and included Holter-ECG, 12-lead ECG and history. Outcome-relevant data from implanted cardiac devices (CIED), such as 2-chamber ICD and pacemakers, or implantable loop recorders were analyzed when available. A predefined subgroup analysis was performed in the following subgroups: first procedure vs. redo procedure, paroxysmal vs. persistent AF, and RF ablation vs. cryoablation. Results The BASE-AF2 (AUC 0.630, p Conclusion Despite numerous available scores, predicting recurrences after AF ablation remains challenging. New simple and robust predictors are needed, potentially based on diagnostic interventions, as well as novel genetic, functional and anatomic parameters.

Background Based on a quality assurance initiative of the German Society for Thoracic and Cardiovascular Surgery (DGTHG) and the German Society for Pediatric Cardiology and Congenital Heart Defects (DGPK), a voluntary registry was founded for assessment of treatment and outcomes of patients with congenital heart disease in Germany. This evaluation by the German Registry for cardiac operations and interventions in patients with congenital heart disease reports the data and the outcome over a 6-year period in patients undergoing invasive treatment. Methods This real-world database collects clinical characteristics, in-hospital complications, and medium-term outcome of patients who underwent cardiac surgical and interventional procedures within the prospective, all-comers registry. Patients were followed-up for up to 90 days. Results In the period from 2013 to 2018, a total of 35,730 patients, 39,875 cases, respectively 46,700 procedures were included at up to 31 German institutions. The cases could be subcategorized according to the treatment intention into 21,027 (52.7%) isolated operations, 17,259 (43.3%) isolated interventions, and 1,589 (4.0%) with multiple procedures. Of these, 4,708 (11.8%) were performed in neonates, 10,047 (25.2%) in infants, 19,351 (48.5%) in children of 1 to 18 years, and 5,769 (14.5%) in adults. Also, 15,845 (33.9%) cases could be allocated to so-called index procedures which underwent a more detailed evaluation to enable meaningful comparability. The mean unadjusted in-hospital mortality of all cases in our registry ranged from 0.3% in patients with isolated interventions and 2.0% in patients with surgical procedures up to 9.1% in patients undergoing multiple procedures. Conclusion This annually updated registry of both scientific societies represents voluntary public reporting by accumulating actual information for surgical and interventional procedures in patients with congenital heart disease (CHD) in Germany. It describes advancements in cardiac medicine and is a basis for internal and external quality assurance for all participating institutions. In addition, the registry demonstrates that in Germany, both interventional and surgical procedures for treatment of CHD are offered with high medical quality.

The global surge in bacterial resistance against traditional antibiotics triggered intensive research for novel compounds, with antimicrobial peptides (AMPs) identified as a promising candidate. Automated methods to systematically generate and screen AMPs according to their membrane preference, however, are still lacking. We introduce a novel microfluidic system for the simultaneous cellfree production and screening of AMPs for their membrane specificity. On our device, AMPs are cell-free produced within water-in-oil-inwater double emulsion droplets, generated at high frequency. Within each droplet, the peptides can interact with different classes of coencapsulated liposomes, generating a membrane-specific fluorescent signal. The double emulsions can be incubated and observed in a hydrodynamic trapping array or analyzed via flow cytometry. Our approach provides a valuable tool for the discovery and development of membrane-active antimicrobials., Angewandte Chemie. International Edition, 61 (13), ISSN:1433-7851, ISSN:1521-3773, ISSN:0570-0833

Axion-like particles (ALPs) are predicted in many extensions of the Standard Model, and their masses can naturally be well below the electroweak scale. In the presence of couplings to electroweak bosons, these particles could be emitted in flavor-changing $B$ meson decays. We report herein a search for an ALP, $a$, in the reaction $B^\pm\rightarrow K^\pm a$, $a\rightarrow\gamma\gamma$ using data collected by the BABAR experiment at SLAC. No significant signal is observed, and 90% confidence level upper limits on the ALP coupling to electroweak bosons are derived as a function of ALP mass, improving current constraints by several orders of magnitude in the range $0.175\,\,\mathrm{GeV} < m_a < 4.78\,\,\mathrm{GeV}$., Comment: 11 pages, 8 figures, submitted to Phys. Rev. Lett