Balloon technologies for pulmonary vein isolation-12-month outcome and comparison of the novel radiofrequency balloon with the cryoballoon in patients with paroxysmal atrial fibrillation.

BACKGROUND: The cryoballoon (CB) has become a standard tool for pulmonary vein isolation (PVI), but the technology is limited in certain ways. A novel RF-balloon (Heliostar™, Biosense Webster, CA, USA) promises the advantages of a balloon technology in combination with 3D mapping. METHODS: To assess procedural data and outcome, all patients undergoing RF-balloon PVI were included and compared with data from consecutive patients undergoing CB PVI for paroxysmal AF. RESULTS: A total of 254 patients (63 ± 13 years, 54% male) were included: 30 patients undergoing RF-balloon and 224 patients CB PVI. Baseline parameters were comparable. Procedure duration (104.3 ± 35.3 min vs. 69.9 ± 23.1 min; p ≤ 0.001) and fluoroscopy time (16.3 ± 7.1 min vs. 11.6 ± 4.9 min; p ≤ 0.001) were longer using the RF-balloon; ablation time (43.5 ± 17.9 vs. 36.4 ± 15.6; p = 0.08) did not differ, and time-to-isolation (TTI) was shorter (18.2 ± 7.0 s vs. 62.8 ± 35.1 s; p ≤ 0.001). Second-generation RF-balloon cases showed shorter ablation time and TTI at comparable procedure duration and fluoroscopy time. One pericardial effusion occurred with the RF-balloon due to complicated transseptal access. During CB PVI in 4/224 patients (1.8%), a phrenic nerve palsy was observed. After 12 months, 78% of patients after RF-balloon and 81% of patients after CB PVI (p = 0.5) were free from atrial arrhythmias. CONCLUSION: The RF-balloon was safe and effective. Compared with the CB, TTI was shorter, but procedure durations and fluoroscopy times were longer. This can be attributed to a learning curve and the initial necessity for separate 3D map preparation. Considering the results with the second-generation RF-balloon, more experience is needed to determine the potential benefits.

The omnipolar mapping technology-a new mapping tool to overcome "bipolar blindness" resulting in true high-density maps.

BACKGROUND: Omnipolar mapping (OT) is a novel tool to acquire omnipolar signals for electro-anatomical mapping, displaying true voltage and real-time wavefront direction and speed independent of catheter orientation. The aim was to analyze previously performed left atrial (LA) and left ventricular (LV) maps for differences using automated OT vs. standard bipolar settings (SD) and HD wave (HDW) algorithm. METHODS: Previously obtained SD and HDW maps of the LA and LV using a 16-electrode, grid-shaped catheter were retrospectively analyzed by applying automated OT, comparing voltage, point density, pulmonary vein (PV) gaps, and LV scar area. RESULTS: In this analysis, 135 maps of 45 consecutive patients (30 treated for LA, 15 for LV arrhythmia) were included. Atrial maps revealed significantly higher point densities using OT (21471) vs. SD (6682) or HDW (12189, p < 0.001). Mean voltage was significantly higher using OT (0.75 mV) vs. SD (0.61 mV) or HDW (0.64 mV, p < 0.001). OT maps detected significantly more PV gaps per patient vs. SD (4 vs. 2), p = 0.001. In LV maps, OT revealed significantly higher point densities (25951) vs. SD (8582) and HDW (17071), p < 0.001. Mean voltage was significantly higher for OT (1.49 mV) vs. SD (1.19 mV) and HDW (1.2 mV), p < 0.001. Detected scar area was significantly smaller using OT (25.3%) vs. SD (33.9%, p < 0.001). CONCLUSION: OT mapping leads to significantly different substrate display, map density, voltage, detection of PV gaps, and scar size, compared to SD and HDW in LA and LV procedures. Successful CA might be facilitated due to true HD maps.

Biological nitrogen fixation, diversity and community structure of diazotrophs in two mosses in 25 temperate forests.

Many moss species are associated with nitrogen (N)-fixing bacteria (diazotrophs) that support the N supply of mosses. Our knowledge relates primarily to pristine ecosystems with low atmospheric N input, but knowledge of biological N fixation (BNF) and diazotrophic communities in mosses in temperate forests with high N deposition is limited. We measured BNF rates using the direct stable isotope method and studied the total and potentially active diazotrophic communities in two abundant mosses, Brachythecium rutabulum and Hypnum cupressiforme, both growing on lying deadwood trunks in 25 temperate forest sites. BNF rates in both mosses were similar to those observed in moss species of pristine ecosystems. H. cupressiforme fixed three times more N2 and exhibited lower diazotrophic richness than B. rutabulum. Frankia was the most prominent diazotroph followed by cyanobacteria Nostoc. Manganese, iron, and molybdenum contents in mosses were positively correlated with BNF and diazotrophic communities. Frankia maintained high BNF rates in H. cupressiforme and B. rutabulum even under high chronic N deposition in Central European forests. Moss N concentration and 15 N abundance indicate a rather minor contribution of BNF to the N nutrition of these mosses.

Comparison of pulsed-field ablation versus very high power short duration-ablation for pulmonary vein isolation.

BACKGROUND: The newly introduced nonthermal pulsed field ablation (PFA) is a promising technology to achieve fast pulmonary vein isolation (PVI) with high acute success rates and good safety features. However, previous studies have shown that very high power short duration ablation (VHPSD) is also highly effective and fast to achieve PVI with potentially less arrhythmia recurrence compared to conventional radiofrequency ablation. Data comparing PFA to VHPSD-PVI is lacking. OBJECTIVE: This study compared procedural and outcome data for PFA-PVI to VHPSD-PVI in patients with paroxysmal or persistent atrial fibrillation (PAF/persAF). METHODS: Consecutive patients undergoing de novo PVI (PFA or VHPSD) were included in this analysis. For PFA-PVI a pentaspline 20 electrode catheter was used. For VHPSD-PVI an enhanced irrigated catheter with a power setting of 70 W/7 s (70 W/5 s at posterior wall) was employed in conjunction with electro-anatomical mapping. All procedures were performed in deep analgo-sedation. RESULTS: A total of n = 114 patients (n = 57[50%] PFA, n = 17[30%] PAF; n = 40[70%] persAF) 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 < 0.01) but longer fluoroscopy time (PFA 15 ± 5 min and VHPSD 12 ± 3 min; p < 0.001). At follow-up after median 125 days (interquartile range: 109-162) n = 46 PFA (80.7%) and n = 44 VHPSD pts (77.2%) were free from atrial arrhythmia after a single procedure (p = 0.819). Two tamponades occurred in the PFA while in VHPSD two pts suffered groin bleedings. One clinically nonsignificant PV stenosis occurred in the VHPSD group. CONCLUSION: Pulsed-field ablation and VHPSD-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. Compared to PFA VHPSD-PVI might ensure information on left atrial substrate allowing to target concomitant secondary tachycardias.

Implementation and first outcomes of a novel standard operating procedure for preprocedural transoesophageal echocardiography screening in course of atrial arrhythmia ablation.

AIMS: Preprocedural transoesophageal echocardiography (TEE) screening for left atrial (LA) thrombi is the standard of care in many centres performing atrial fibrillation (AF) ablation. However, TEE imposes procedural risks for patients and is often challenging to implement in daily practice, besides causing patient discomfort. At our centre, a novel standard operating procedure (SOP) was implemented, aiming to identify patients that can be exempt from TEE screening. We aimed to assess whether this screening approach may reduce preprocedural TEEs without imposing patients of higher risks for cerebrovascular events (CVEs). METHODS AND RESULTS: Data of 1874 consecutive patients treated by catheter ablation of LA arrhythmias between 2018 and 2022 were retrospectively analysed. A cohort of 937 patients, where decision to perform TEE screening was based on a new SOP (considering rhythm at admission, CHA2DS2-VASc score, and sufficient anticoagulation), was compared to a matched cohort receiving TEE before every procedure. Number of performed TEEs and incidences of CVEs were compared. Implementation of the new SOP led to a 67% reduction in TEEs performed (old SOP: 933 vs. new SOP: 305). No significant differences between the groups were detected regarding transitory ischaemic attack (old SOP: 5 vs. new SOP: 3; P = 0.48) and stroke (no events). No solid thrombi were detected during TEE screening. CONCLUSION: The number of preprocedural screening TEEs before AF ablation procedures can be safely reduced by applying risk stratification based on rhythm at admission and CHA2DS2-VASc score, if anticoagulation was performed properly.

Comparison of pulsed field ablation and cryoballoon ablation for pulmonary vein isolation.

INTRODUCTION: Pulmonary vein isolation (PVI) remains the cornerstone in the treatment of atrial fibrillation (AF). PVI using cryoballoon (CB) technology has emerged as a standard procedure in many centers. Recently, pulsed field ablation (PFA) has been introduced and used to achieve PVI. First data show high acute and favorable long-term outcomes. So far, data comparing these new "single shot" devices are sparse. We sought to compare procedural and outcome data for first time PFA users versus CB in patients undergoing de novo PVI. Furthermore, potentially postprocedural discomfort and affection of autonomic ganglia were assessed. METHODS AND RESULTS: A retrospective analysis and comparison of all de novo PVIs with PFA and CB was performed. Furthermore, PFA PVI learning curve was evaluated. During follow-up, repeat outpatient visits and Holter electrocardiogram were performed to analyze arrhythmia-free survival. Discomfort analysis was obtained by prescribed analgesic medication within first 48 h after PVI. Potential changes in heart rate (HR) between baseline and at 3-month follow-up were evaluated. A total of 108 patients (54 PFA and 54 CB; PFA; 33 (30%) female) with paroxysmal and persistent AF were analyzed. Type of AF was comparable (Patients suffering from PAF: PFA: 16 (30%), CB: 17 (31%), p = 1.0). In 107 (99%) patients, successful PVI was achieved. Transient phrenic palsy omitted complete PVI in one CB patient. A trend for a shorter overall procedure duration was observed in the PFA group (PFA: 64.5 ± 17.5 min; CB: 73.0 ± 24.8 min; p = 0.07). Excluding LA mapping time (first 14 cases), procedure time was significantly shorter using PFA (PFA: 58.0 ± 12.5 min, CB: 73.0 ± 24.8 min, p = 0.0001). Fluoroscopy time was significantly longer for PFA (PFA: 15.3 ± 4.7 min, CB: 12.3 ± 5.3 min; p = 0.001), but significantly less contrast medium was used (PFA: 12 ± 6 mL; CB: 51 ± 29 mL, p < 0.0001). Subgroup analysis of the PFA group revealed a significant shortening of procedure duration over time (first tertile: 72.7 ± 13.5 min, second tertile: 67.3 ± 21.7 min, third tertile: 53.4 ± 9.8 min, first vs. third tertile p < 0.0001). Two cardiac tamponades occurred in the PFA group (p = 0.495), of which one was most likely related to complex transseptal puncture. In the first 48 h after PVI, the number of prescribed analgesics due to postprocedural pain was equal between both groups (PFA: 7 (13%) patients, CB: 10 (19%) patients, p = 0.598). After a FU of 273 ± 129 days, 35 of 47 patients (74%) after PFA and 36 of 50 patients (72%) after CB PVI were free of any atrial arrhythmia (HR: 0.98, p = 0.88). Only in the PFA group, a significant increase in HR 3 months after PVI was observed (pre-PVI: 61 ± 8 beats/min, post-PVI: 65 ± 9 beats/min, p = 0.008). CONCLUSION: The new PFA technology is equally effective and safe as compared to CB for complete PVI with potentially shorter procedure time and significantly less contrast medium. However, AF recurrence rates after PFA PVI seem to be comparable to CB PVI.

First long-term outcome data for the MicraVR™ transcatheter pacing system: data from the largest prospective German cohort.

AIMS: The MicraVR™ transcatheter pacing system (TPS) has been implemented into clinical routine for several years. The primary recipients are patients in need for VVI pacing due to bradycardia in the setting of atrial fibrillation (AF). Implantation safety and acute success have been proven in controlled studies and registries. So far only few long-term real-life data on TPS exist. We report indication, procedure and outcome data from two high-volume implanting German centers. METHODS: Between 2016 and 2019, 188 (of 303) patients were included. During follow-up (FU), TPS interrogation was performed after 4 weeks and thereafter every 6 months. RESULTS: Indication for TPS implantation in 159/188 (85%) patients was permanent or intermittent AV block III° in the setting of atrial fibrillation. The mean procedure duration was 50 min [35.0-70.0]. The average acute values after system release were: thresholds: 0.5V [0.38-0.74]/0.24ms; R-wave sensing: 10.0mV [8.1-13.5]; impedance: 650 Ohm [550-783]; RV-pacing demand: 16.9% [0.9-75.9]; and battery status: 3.15 V [3.12-3.16]. During FU of 723.4 ± 597.9 days, neither pacemaker failure nor infections were reported. Long-term FU revealed: thresholds: 0.5V [0.38-0.63]/0.24 ms; sensing: 12.3mV [8.9-17.2]; impedance: 570 Ohm [488-633]; RV-pacing demand: 87.1% [29.5-98.6]; and battery status 3.02 V [3.0-3.1]. Forty-three patients died from not-device-related causes. CONCLUSION: This to date largest German long-term dataset for MicraVR™ TPS implantation revealed stable device parameter. Foremost, battery longevity seems to fulfill predicted values despite a significant increase in RV-pacing demand over time and even in patients with consecutive AV-node ablation. Of note, no infections or system failure were observed.

Lakeshore vegetation: More resilient towards human recreation than we think?

Lakes and their shoreline vegetation are rich in biodiversity and provide multiple functions and habitats for fauna and flora. Humans are attracted by the scenic beauty of these ecosystems and the possibilities for recreational activities they offer. However, the use of lakes for recreational activities can lead to disturbance of vegetation, threatening the integrity and functionality of shoreline areas. Recent literature reviews revealed that impacts of the seemingly harmless activities bathing and lingering on the shore on lakeshore vegetation are poorly understood. In this study, we analysed the effects of shoreline use connected with bathing on the structure, composition and diversity of lakeshore vegetation. Vegetation relevés were recorded in 10 bathing and 10 adjacent control sites in the nature park 'Dahme-Heideseen' (Brandenburg, Germany). In addition visitor counts were performed. The species composition and the cover of herbaceous and shrub vegetation differed between bathing and control sites, but all sites had a high percentage of plant species not typical for the community. The vegetation parameters did not correlate with visitor counts. The results indicate that the present visitor intensity in the nature park does not impact the vegetation severely.

Pulmonary vein isolation for atrial fibrillation using true high-power short-duration vs. cryoballoon ablation.

AIMS: Pulmonary vein isolation (PVI) is achievable and effective using radiofrequency (RF) catheter (CA) or cryoballoon (CB) ablation. The newly introduced high RF-power short-duration ablation (HPSD) technique has shown promising results. Data comparing HPSD- to CB-PVI is sparse. We sought to investigate success rates and procedural differences of HPSD-PVI vs. CB-PVI in patients undergoing ablation for PAF and persAF. METHODS: Consecutive patients undergoing de novo PVI (HPSD or CB) were included. A power setting of 70W/7 s (70W/5 s at posterior wall) using a flexible tip catheter with enhanced irrigation was considered as true HPSD. Follow-up consisted of out-clinic pts visits, tele-consultation, 48-h Holter ECG, app-based telemonitoring and cardiac implanted electronic devices (CIED) interrogation. RESULTS: 721 patients (46 HPSD, 675 CB) were analyzed. In all HPSD (27 persAF [59%]) and CB patients (423 persAF [63%]), PVI was successfully achieved. Procedure duration was significantly longer for HPSD (91 ± 19 min vs. 72 ± 18 min, p < 0.01). Ablation time was similar in both groups (HPSD: 44 ± 19 min vs. CB: 40 ± 17 min; p = 0.347). No major complications occurred in HPSD. For CB-PVI, in 25 (3.7%; p = 0.296) patients, complications occurred. At a follow-up of 290 ± 135 days, arrhythmia-free survival using HPSD was non-inferior to CB-PVI in the Kaplan-Meier survival analysis (p = 0.096). CONCLUSION: PVI using HPSD is equally effective and safe to CB-PVI. This analysis revealed a similar arrhythmia-free survival after HPSD and CB with low complication rates. Procedure duration for CB was significantly shorter while LA dwell time excluding mapping was equal. Currently, a prospective trial is conducted to corroborate these findings.

Regeneration in European beech forests after drought: the effects of microclimate, deadwood and browsing.

With progressing climate change, increasing weather extremes will endanger tree regeneration. Canopy openings provide light for tree establishment, but also reduce the microclimatic buffering effect of forests. Thus, disturbances can have both positive and negative impacts on tree regeneration. In 2015, three years before an extreme drought episode hit Central Europe, we established a manipulation experiment with a factorial block design in European beech (Fagus sylvatica L.)-dominated forests. At five sites located in southeastern Germany, we conducted three censuses of tree regeneration after implementing two different canopy disturbances (aggregated and distributed canopy openings), and four deadwood treatments (retaining downed, standing, downed + standing deadwood and removing all deadwood), as well as in one untreated control plot. In addition, we measured understory light levels and recorded local air temperature and humidity over five years. We (i) tested the effects of experimental disturbance and deadwood treatments on regeneration and (ii) identified the drivers of regeneration density as well as seedling species and structural diversity. Regeneration density increased over time. Aggregated canopy openings supported species and structural diversity, but reduced regeneration density. Tree regeneration was positively associated with understory light levels, while maximum vapor pressure deficit influenced tree regeneration negatively. Deadwood and browsing impacts on regeneration varied and were inconclusive. Our study indicates that despite the drought episode regeneration in beech-dominated forests persisted under moderately disturbed canopies. However, the positive effect of increased light availability on tree regeneration might have been offset by harsher microclimate after canopies have been disturbed. Supplementary Information: The online version contains supplementary material available at 10.1007/s10342-022-01520-1.

Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes.

Introduction: Genetic disorders are among the most prevalent causes leading to progressive glomerular disease and, ultimately, end-stage renal disease (ESRD) in children and adolescents. Identification of underlying genetic causes is indispensable for targeted treatment strategies and counseling of affected patients and their families. Methods: Here, we report on a boy who presented at 4 years of age with proteinuria and biopsy-proven focal segmental glomerulosclerosis (FSGS) that was temporarily responsive to treatment with ciclosporin A. Molecular genetic testing identified a novel mutation in alpha-actinin-4 (p.M240T). We describe a feasible and efficient experimental approach to test its pathogenicity by combining in silico, in vitro, and in vivo analyses. Results: The de novo p.M240T mutation led to decreased alpha-actinin-4 stability as well as protein mislocalization and actin cytoskeleton rearrangements. Transgenic expression of wild-type human alpha-actinin-4 in Drosophila melanogaster nephrocytes was able to ameliorate phenotypes associated with the knockdown of endogenous actinin. In contrast, p.M240T, as well as other established disease variants p.W59R and p.K255E, failed to rescue these phenotypes, underlining the pathogenicity of the novel alpha-actinin-4 variant. Conclusion: Our data highlight that the newly identified alpha-actinin-4 mutation indeed encodes for a disease-causing variant of the protein and promote the Drosophila model as a simple and convenient tool to study monogenic kidney disease in vivo.

Dipole Density Guided Catheter Ablation versus Conventional Substrate Modification for Repeat Catheter Ablation of Persistent Atrial Fibrillation.

AIMS: The optimal ablation strategy for recurrent persistent atrial fibrillation (persAF) after initially successful catheter ablation (CA) remains debatable. Dipole density (DD) guided CA using the AcQMap system has been proven to be feasible and effective in patients with persAF. So far, long-term outcome data for DD-guided CA in patients with recurrence of persAF are sparse. This study sought to assess long-term outcome data in patients undergoing a DD-guided CA for recurrence of persAF after previous CA in comparison to conventional repeat CA. METHODS AND RESULTS: Patients undergoing DD-guided CA for recurrence of persAF after previous ablation were compared to patients undergoing conventional substrate modification (CSM). A total of 64 patients (32 DD-guided and 32 CSM) were included in this analysis. Procedure duration (DD: 236 ± 61 min; CSM: 198 ± 59 min; p = 0.004) and fluoroscopy time (DD: 36 ± 15 min; CSM: 20 ± 11 min; p = 0.0001) were significantly longer in the DD group. After a long-term median follow-up (FU) of 27 months (interquartile range 12.8-34.3), DD-guided CA was inferior to CSM regarding overall arrhythmia-free survival (DD: 6 patients (19%), CSM: 11 patients (34%); HR 1.47; p = 0.04). Freedom from AF did not differ between both groups (DD: 16 patients (50%); CSM: 18 patients (56%), HR 0.99, p = 0.47). During FU, more patients underwent repeat CA after DD-guided ablation (DD: 16 patients (50%), CSM: 7 patients (22%), p = 0.04). No major complications occurred overall. CONCLUSIONS: Dipole density-guided CA is equally safe but associated with longer procedure duration compared to conventional substrate modification for treatment of recurrent persAF after previous CA. Of note, long-term arrhythmia-free survival is significantly worse after DD-guided ablation, and more patients undergo redo procedures.

Procedural and outcome impact of obesity in cryoballoon versus radiofrequency pulmonary vein isolation in atrial fibrillation patients.

PURPOSE: Cryoballoon (CB) ablation and radiofrequency (RF) ablation are the most common techniques for pulmonary vein isolation (PVI) in patients with symptomatic atrial fibrillation (AF). An increasing number of patients undergoing PVI are obese. To address the paucity of data on outcomes of CB- vs. RF-based PVI in relation to body mass index (BMI) of AF patients. METHODS: All patients undergoing de novo PVI between 01/2018 and 08/2019 at University Hospital Cologne were included in this retrospective analysis. Patients of each group (CB-PVI vs. RF-PVI) were analyzed based on their BMI. Hereafter, procedural characteristics and AF recurrence rate were compared regarding different BMI groups. RESULTS: A total of 526 patients (62% male, 65±11 years) underwent successful de novo PVI (320 CB and 206 RF). In obese patients, two differences in procedural characteristics were noted: A significantly increased contrast medium volume in CB group and a lower fluoroscopy dose in RF group: contrast medium: CB 50 [40-80] vs. RF 20 [20-30], p<0.001; fluoroscopy dose: CB 392.4 [197.9-995.9] vs. RF 282.5 [139.8-507.2], p<0.001. The complication rate was equal throughout all BMI groups, regardless of CB or RF usage. For obese patients, a trend toward a higher AF recurrence rate was revealed after RF-PVI as compared to CB-PVI. In line with previous studies, the overall procedure time was significantly shorter with CB-PVI regardless of BMI. CONCLUSION: For obese patients, 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 and RF-PVI.

Validation of seven risk scores in an independent cohort: the challenge of predicting recurrence after atrial fibrillation ablation

Purpose@#Several predictive scores for atrial fibrillation (AF) recurrence after AF ablation have been developed. We compared the predictive value of seven previously described risk scores ((CHADS 2 and ­CHA 2 DS 2 -VASC, HATCH, APPLE, CAAP-AF, BASE-AF2, MB-LATER) for prediction of AF recurrence risk at 12 months after AF ablation in our patient cohort. Further, we aimed to identify additional variables to predict recurrences after AF ablation. @*Methods@#We used data from our digital AF ablation registry to compare the previously published scores in an independent cohort (n = 883, 50.8% with paroxysmal AF). The scores were chosen based on earlier publications and availability of relevant data. @*Results@#The BASE-AF2 (AUC 0.630, p < 0.001), MB-LATER (AUC 0.612, p < 0.001), CAAP-AF (AUC 0.591, p < 0.001), APPLE (AUC 0.591, p < 0.001) and CHA2DS2-VASC (AUC 0.547, p = 0.018) scores had a statistically significant but modest pre‑ dictive value for 12-month AF recurrence. None of the scores were significantly superior. Other analyzed scores had no predictive value. There was no difference in the predictive value for 12-month recurrence of AF between first pro‑ cedure vs. redo procedure and RF ablation vs. cryoablation. Unlike other scores, MB-LATER showed better predictive value for paroxysmal vs. persistent AF (AUC 0.632 vs. 0.551, p = 0.038). In the multivariate logistic regression, only age (p = 0.006), number of prior electrical cardioversions (p < 0.001) and early AF recurrence (p < 0.001) were independent predictors of AF recurrence. @*Conclusion@#Despite numerous available scores, predicting recurrences after AF ablation remains challenging. New predictors are needed, potentially based on interventions, as well as novel genetic, functional and anatomic parameters.

[A patient with second-degree AV block-further work-up and treatment]. / Ein Patient mit AV Block II°­ weitere Diagnostik und Therapie.

We present the case of a 64-year-old man who presented to our outpatient clinic with intermittent palpitations and presyncopal events. In 2009, he underwent dual chamber pacemaker implantation in another institution for 2nd degree heart block. Pharmacological treatment attempts with ß­blocker, calcium channel antagonists and ivabradine remained clinically unsuccessful. Up to this point in time, no documentation of clinical tachycardia, which was reported to result in a heart rate of around 160 beats/minute, was obtained. The patient presented to our clinic for further electrophysiological evaluation.

Mapping strategies for premature ventricular contractions-activation, voltage, and/or pace map.

A high premature ventricular contraction (PVC) burden is associated with an increase in cardiovascular mortality and may become clinically apparent through palpitations, reduced physical capacity or PVC-induced cardiomyopathy. Catheter ablation has been shown to be a more effective tool to treat patients with a high PVC burden than medical therapy alone. Current recommendations list catheter ablation as a class I option in patients with symptomatic idiopathic outflow tract PVCs as well as in patients with suspected PVC-induced cardiomyopathy. Careful planning is necessary to maximize efficiency and outcome of the ablation procedure. Prediction of the most likely PVC origin by studying the 12-lead electrocardiogram (ECG) is important. A high burden of spontaneous PVCs is associated with a better outcome during and after the procedure; pharmacological provocation can be performed. Developments in high density mapping systems have greatly advanced accuracy and efficiency of arrhythmia mapping in recent years. Different systems are now available that allow the simultaneous use and integration of different mapping information in an automated manner. Voltage mapping, activation mapping and pace mapping are used in clinical practice today. Activation mapping is used to visualize the area of earliest activation. While it is a very accurate tool, it relies on a high burden of spontaneous PVCs. Pace mapping aims to find the target area by means of stimulation and comparison of paced QRS complexes with the clinical PVC. Today, mostly a combination of both methods is used to maximize procedure outcome and efficiency. While voltage mapping plays a primary role in the mapping of substrate-based sustained arrhythmias in patients with underlying structural heart disease, activation and pace mapping are the methods of choice for PVC mapping.

Quantification of molecular heterogeneity in kidney tissue by targeted proteomics.

Renal diseases are driven by alterations in the entity of proteins within the kidney, at the level of single cells, nephron subunits (such as glomerulus and tubule), tissues and body fluids. Histologically, kidney diseases are extremely heterogeneous. Mass-spectrometry based proteomics provides a unique opportunity to interrogate heterogeneity and dynamics of various proteome layers within the kidney to better understand physiology and pathophysiology, and to translate signaling networks into therapies. Yet, the success of this endeavor will largely depend on improving proteomic data acquisition methods toward increased reproducibility. Here, we provide an overview of targeted proteomics studies in renal tissue and their insights into major renal diseases such as diabetic nephropathy, acute kidney injury and chronic kidney disease. The technical approaches currently include antibody-based and mass spectrometry based approaches, range from single-cells to single-nephrons to bulk tissue proteomic acquisitions, and are applied to physiological studies and translational approaches in biomarker discovery. Within this context, we identify key challenges in proteomics of kidney biopsies. We also suggest that novel models of translational nephrology have increased need for targeted acquisition of proteomics data with focus on primary urinary cells, organoids and induced renal epithelial cells (IRECs). In conclusion, targeted proteomics will be very beneficial to identify heterogenic disease mechanisms that drive renal disease and further emerge as an important tool in translational kidney research. SIGNIFICANCE: Improved targeted proteomics technologies will be an important cornerstone of renal systems medicine in order to identify and tackle the heterogenic disease mechanisms driving renal disease.

A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes.

Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease-susceptible conditions. Integration of acquired omics dimensions suggested FARP1 as a candidate essential for podocyte function, which could be substantiated by genetic analysis in humans and knockdown experiments in zebrafish. This work exemplifies how the integration of multi-omics datasets can identify a framework of cell-type-specific features relevant for organ health and disease.

Efficacy of photodynamic therapy as adjunct treatment of chronic periodontitis: a systematic review and meta-analysis.

Meta-analysis of treatment effects of antimicrobial photodynamic therapy (aPDT) adjunct to non-surgical scaling and root planing (SRP) in comparison to SRP alone on patients with chronic periodontitis. The meta-analysis was performed according to PRISMA statement and Cochrane Collaboration guidelines. Electronic search complemented by hand search assured a high yield of randomized controlled trials (RCTs) of aPDT as adjunct modality to SRP. Differences in probing depth (PD) and clinical attachment level (CAL) were calculated with 95% confidence intervals and pooled in a random effects model. Analysis for intra- and inter-study heterogeneity was provided by χ 2 and I 2 tests, and publication bias was checked by funnel plots. Pooled overall effects of 26 RCTs attested significant benefits of aPDT adjunct to SRP with respect to PD reduction (MD 0.37; 95% CI 0.12-0.53; P < 0.0001) and CAL gain (MD 0.33; 95% CI 0.19-0.48; P < 0.00001) after 3 and 6 months. Sensitivity analysis minimized heterogeneity of PD reduction (MD 0.21; 95% CI 0.13-0.30; P < 0.00001) and CAL gain (MD 0.36; 95% CI 0.27-0.46). aPDT adjunct to SRP provides significant PD reduction and CAL gain in treatment of chronic periodontitis. This moderate effect was found after 3 and 6 months which is short from a clinical perspective.