Abstract Background Pulsed field ablation (PFA) is an emerging method for catheter ablation of atrial fibrillation (AF). Data comparing efficacy and safety of PFA compared to thermal ablation is still scarce. In this study, we compared a cohort of patients who underwent PFA with those who received very high power short duration (vHPSD) radiofrequency catheter ablation at the University Hospital Graz. Methods We analysed baseline data from both cohorts (PFA: n=231; RF: n=243). Both procedures were performed under deep sedation, using propofol and fentanyl. The PFA procedure involved 2x2x2 pulses, with additional pulses as required. RF procedures were performed using the QDOT Micro catheter to deliver 90 watts of energy over 4 seconds. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 29. The Kruskal-Wallis test was used for quantitative non-parametric data in the baseline analysis, and the Man-Whitney-U test was used for quantitative non-parametric procedural data. For qualitative variables the Chi-squared test was used. A p-value of less than 0,05 was considered significant. Results Both groups were similar, apart from chronic heart failure, which was more prevalent in the RF group (p=0.003). Mean age for both groups was 62±10 years and mean body mass index did not differ as well. CHADS-VASc score was 2±2 in the RF and 2±1 in the PFA group (p=0.7). The types of AF were distributed as follows: (RF vs.PFA): PAF: 64%/61%; persAF: 34/36%; long standing persAF: 2%/3%. As to this date performing a CTI line with PFA is off-label, a significantly higher number of patients with additional flutter were ablated in the RF group. In the RF-group, 91 patients underwent additional cavotricuspid isthmus ablation, compared to only 14 patients in the PFA group (p<0.001). Procedural time (RF:PFA 122±min:57±26min; p<0.001), fluoroscopy time (RF:PFA 15±9min:19±9min; p<0.001) and fluoroscopy dose (RF:PFA 17±40Gycm2:15±15Gycm2, p=0.026) showed significant differences, with procedural time and fluoroscopy dose presenting lower values in the PFA group. First pass isolation was achieved more frequently in the PFA group (85% vs. 57%; p<0,001). There was significant difference in recurrence rates between the vHPSD and PFA groups (RF: 56/242 (28%), PFA: 38/231 (17%); p=0.005). Additionally, time to recurrence in the RF group was 138±117 days, compared to 166±84min in the PFA group. We exclude operator dependence as the same operators performed both procedures. Conclusion Based on our findings, PFA could potentially become the standard procedure for many patients. However, randomized trials are needed to confirm these findings.

The efficacy of dermal drugs strongly depends on the free drug fraction in the skin which is accessible by sampling dermal interstitial fluid (dISF). The free drug fraction in the dISF is influenced by the drug's protein binding properties and the amount of protein present. As inflammation can alter the protein content in dISF, it will also influence protein binding and subsequently the free drug fraction and drug efficacy. This study aimed to determine the concentration of the main binding proteins in dISF namely albumin and α1-acid glycoprotein (AGP) in normal and inflamed pig skin. Inflammation was assessed by using IL-6. In a preclinical study in landrace pigs (n=3, female, 10 weeks), we collected diluted dISF samples by standard dermal open flow microperfusion (dOFM) and pure dISF samples by dOFM recirculation (30 recirculations over 12 h) in normal and inflamed skin. Inflammation was induced by treating split thickness wounds with resiquimod for 2 days. IL-6 concentrations were assessed in normal (n = 12) and inflamed (n = 12) skin sites. Albumin and AGP absolute concentrations were quantified using dISF samples from normal (n = 6) and inflamed (n = 11) skin sites. Mean IL-6 concentration in inflamed skin (10.8 ± 4.6 ng/ml) was significantly higher than in normal skin (0.4 ± 0.2 ng/ml). Mean absolute protein concentrations were higher in inflamed skin (albumin: 19.0 ± 6.9 mg/ml, AGP: 0.56 ± 0.13 mg/ml) than in healthy skin (albumin: 11.0 ± 1.3 mg/ml, AGP: 0.31 ± 0.06 mg/ml). These findings indicate that higher protein concentrations in inflamed skin may result in higher protein binding and can thus be of crucial importance for drug development for inflammatory skin diseases, especially for highly protein bound drugs. This research was funded by the Austrian Federal Ministry of Climate Action, Environment, Energy, Mobility, Innovation and Technology.

The clinical efficacy of dupilumab for treatment of atopic dermatitis (AD) has been proven in several clinical studies. Being an IL4 receptor alpha antagonist dupilumab inhibits IL4- and IL13-signaling. However, the affected mechanisms and differential effects in the dermis compared to blood are not well understood as most studies have been conducted with plasma. Dermal open flow microperfusion (dOFM) provides the unique possibility to collect interstitial fluid (ISF) directly from the dermis and to assess the whole spectrum of ISF components such as cytokines and immune cells. Therefore, we aimed to evaluate the feasibility of dOFM to assess local tissue response after dupilumab treatment by measuring cytokine concentrations and immune cell populations in dermal ISF of lesional and non-lesional skin of AD patients. This exploratory clinical study involved eight patients with moderate to severe AD. Before and after 16 weeks of biweekly dupilumab injections, different cytokines and immune cell populations were assessed from plasma and ISF samples. ISF was collected from lesional and non-lesional skin using dOFM. Clinical treatment effects were assessed using the clinical scores SCORAD, EASI, IGA. Several cytokines such as IL33, IL1B, CXCL8 were quantifiable in ISF, whereas in plasma they were below the lower limit of quantification. Post-treatment IL4 concentrations were increased in plasma and in dermal ISF as a result of blocked receptors, while post-treatment IL5 concentrations, with IL5 being a downstream biomarker from IL4, were decreased only in lesional skin. Immune cell population analysis showed trends reflecting those of cytokines. Clinical scores were significantly smaller post-treatment, confirming the observed immune cell and cytokine changes of dupilumab. In conclusion, results showed that dOFM was able to monitor local tissue response after dupilumab treatment, thus contributing to gain insights into the mechanism of action of dupilumab. The trial was funded by Sanofi (SGZ-2018-12008).

Abstract Background Pulsed field ablation (PFA) is an emerging method for the ablation of atrial fibrillation (AF). As there are few data on incidence, types, and predictors of AF recurrence after PFA for AF ablation, we are continuously analysing our cohort. Methods We report our outcome data after PVI with PFA. Each procedure was performed under deep sedation with propofol and fentanyl. Before transeptal puncture, unfractionated heparin was administered to maintain an ACT level >300sec throughout the procedure. Isolation of pulmonary veins was started after administration of 1mg of atropine with 8 applications per vein (4 in basket, 4 in flower configuration). In recent months we have routinely performed 2 additional ablations in flower configuration with an anterior twist at both right pulmonary veins. All veins were checked for entrance- and exitblock to confirm isolation in sinus rhythm. An additional ablation was performed if necessary. Results In total, 231 patients were analysed. Mean age was 62±10 years, 38% were female. Mean CHADS-VASc score was 2±1. 61% had paroxysmal AF (PAF), 36% persistent AF, and 3% patients had long-standing persistent AF. In 85% (n=197) first-pass isolation of all veins was possible. Primary PV isolation was achieved in all patients at the end of the procedure. In addition to PVI, the cavo-tricuspid isthmus (CTI) was blocked in 6% (using radiofrequency ablation in case of previously or during the procedure documented typical flutter) and the posterior wall was isolated in another 6% during the first procedure. Mean procedure time was 60±20 minutes (24-175 minutes), mean X-ray time 19±9 minutes. In 231 procedures, only two catheter-associated complications were documented. 38 patients (16%) had arrhythmia recurrence after a blanking period of 3 months and a mean follow-up of 273±177 days. Mean time to recurrence was 171±84 days. Women were more likely to have recurrences [OR 2.042 (CI 95% 1.012-4.121), p<0,05]. Patients who had undergone any type of cardiac surgery prior to ablation were also significantly more likely to have recurrence [OR 0.517 (CI 95% 0.116-0.212); p<0.001]. Patients with no other comorbidities were more likely to remain free from arrhythmias [OR 0.792 (95% CI 0.736-0.853); p<0,01]. The type of AF did not make a significant difference according to the risk of recurrence in this cohort. To date, we have performed 18 re-do procedures in patients after PVI with PFA. The recurrent arrhythmia was AF in 39% (n=7), atypical AT in 50% (roof-dependent: 28%, n=5; mitral isthmus dependent: 22%, n=4), and CTI-dependent flutter in 39% (n=7). All but one patient had PV reconnections, and all were successfully reablated. Conclusion PFA success rate is similar to that of thermal techniques. Procedure time is shorter in experienced operators and the complication rate is low in our cohort. Results from RCTs are needed to further evaluate this new method compared to other ablation techniques.

Abstract Funding Acknowledgements Type of funding sources: None. Background Catheter ablation of atrial fibrillation is (AF) an established second line therapy for patients with symptomatic paroxysmal (PAF) and persistent AF (persAF). Novel ablation catheters with integrated thermocouples allow fast application of radiofrequency lesions with powers up to 90W. We aimed to describe primary and secondary outcomes after very high-power short duration (vHPSD) ablation. Methods 201 consecutive patients (127 PAF, 68 persAF, 6 longstanding persistent AF) underwent pulmonary vein isolation (PVI) using the QDOT Micro Catheter (Biosense Webster) with the ablation mode QMODE+ (90W, 4s, interlesion distance ≤4mm anterior, ≤6mm posterior). Results Mean age was 62±10 years, 38% were female, median CHA2DS2-VASc Score was 2 (0, 7). Median follow up duration was 196 (30, 461) days. 35% of patients had additional ablation of typical right atrial flutter. Primary success rate to achieve pulmonary vein isolation was achieved in all patients, no catheter-related complications (e.g., charring, steam pop) occurred. First pass isolation of all 4 PVs was achieved in 53% of patients, re-ablations were necessary in the carina regions (right: 27% of cases, left: 20%), 34% at multiple regions including the ridge, 12% in other regions around the PVs. Median procedure for PVI only were 110 (36-344) minutes. Arrhythmia-free survival was 79,3%. 21 patients underwent re-do procedures during follow-up showing most commonly showing gaps in the right PVs (RSPV 52%, RIPV 43%), the left inferior PV (48%), as well as the LSPV (38%) and the ridge (24%); with 91% of patients with recurrence showing more than one site reconnected. Conclusion Very high-power short duration ablation allows safe and quick pulmonary vein isolation. However, first pass isolation rate is low due to gaps in the carina regions. Arrhythmia-free survival is comparable to other pulmonary vein isolation techniques.

Abstract Funding Acknowledgements Type of funding sources: None. The incidence of early atrial fibrillation (AF) recurrence within the first week after AF ablation and its predictive value for late AF recurrences are unclear. TeleCheck-AF is a remote on-demand mobile health (mHealth) infrastructure, which is based on a mobile phone app using photoplethysmography (PPG) technology (Fibricheck) allowing rate and rhythm monitoring through teleconsultations. The feasibility and clinical implications of PPG telemonitoring specifically during the first week after atrial fibrillation ablation is unknown. Methods Within the TeleCheck-AF project, the Medical University offered a total of 382 consecutive patients undergoing AF ablation (between June 1st 2020 and December 15th 2021) photoplethysmography (PPG) telemonitoring with "FibriCheck" during the first week after the ablation procedure. Patients received a QR code for activation of the software on their smartphone and were connected to the clinician’s telemedicine portal. They were instructed to perform rhythm monitoring three times per day and in case of symptoms. Clinicians assessed the tracings and contacted the patients if therapeutic steps were indicated. Results In total, 119 patients (31%) agreed to perform telemonitoring after ablation. Patients undergoing telemonitoring were younger compared to those who refused participation (58±10years vs. 62±10years, p<0.001). 34% were female, median CHA2DS2-VASc-Score was 1 (0-6). 62% of patients had paroxysmal AF and 37% had persistent AF. One of four patients (24%) had already undergone previous ablations. Most index ablations were radiofrequency ablations (89%; 7% cryo; 4% pulsed field ablation). Median follow up duration was 281 (16-620) days. 27% of patients had tracings suggestive of AF in the week following the index ablation. Telemonitoring resulted in clinical interventions ins 24% of patients: amiodarone was started in 8%, class I antiarrhythmic drugs were up titrated in 7%, cardioversion was scheduled in 5%, antiarrhythmic drugs were reduced due to symptomatic bradycardia in 3% of patients. During follow-up, 22% of patients had ECG-documented AF recurrences. PPG recordings suggestive of AF in the week after ablation were predictive of late recurrences (p<0.001). Conclusion Rhythm monitoring with a PPG-based mHealth application was feasible and often resulted in clinical interventions. Due to its high availability, PPG-based follow-up actively involving patients after AF ablation may close a diagnostic and prognostic gap and increase active patient-involvement. Figure 1: Schematic overview of the telemonitoring process. After the ablation, the patient measures PPGs for one week, dashboard view for clinician shows regular rhythm (green, atrial fibrillation (red) and unclear tracings (blue).

Abstract Funding Acknowledgements Type of funding sources: None. Background Electric conduction disturbances are very common, however, patients in need for ventricular pacing may suffer from pacing-induced heart failure due to unphysiological pacing by the right ventricular lead. Conducting system pacing allows to overcome this common issue with a more physiologic approach, but real-life procedural data using this technology is scarce. Methods We report a single centre experience of the first 63 consecutive patients being implanted with a His-bundle-based pacemaker 09/2020-11/2022 per 3D-mapping guided implantation due to bradyarrhythmia, or for cardiac resynchronisation therapy in heart failure combined with a left-ventricular lead (HOT-CRT) ± a right ventricular defibrillator lead. The identification of the His-bundle-location was done with a 3D electroanatomic mapping system via an introducing sheath that is provided with electrodes at its tip. Results Mean age was 71 [18;87] years, 18/63 (29%) patients were female, mean baseline LVEF was 46±15%. Baseline ECG was captured before implantation: QRS width was 127±34ms, with typical LBBB in 19/63 (30%), typical RBBB in 5/63 (8%), alternating BBB in two patient (3%) and either no BBB or ventricular escape rhythm in 37/63 (59%). Indications for implantation were AV-block grade II-III in 31/63 (49%), primary prophylactic ICD indication in HFrEF in 18/63 (29%), atrial fibrillation with bradycardic conduction in 8/63 patients (13%), sick-sinus-syndrome in 4/63 (7%) and secondary prophylactic ICD indication in one patient (2%). In 57/63 (90,5%) a primary device was implanted, in 6/63 (9,5%) a pre-existent device was upgraded with a HB lead. Therefore, 23 dual-chamber-pacemaker, 5 single-chamber-pacemaker, 10 single-chamber CRT-P, 17 dual-chamber CRT-P, 4 single-chamber CRT-D, 4 dual-chamber CRT-D were implanted. In 63 patients his bundle pacing was attempted, while in 6/63 (9%) patients outside of this analysis the attempt was not successful, these patients were consecutively implanted with a non-HBP-device and therefor excluded from the further analysis. In the 63 patients included in this analysis with a primary successful pacing at the his-position, 5/63 (8%) his-bundle-leads dislocated within the first 48 hours, leading to a secondary success rate of 92%. There were two post-procedural pneumothorax that needed drainage, no major procedure-related complications occurred. Median skin-to skin procedure time was 111±47 minutes in his-bundle-device-implantation. The paced QRS width at the post-implantation follow up was 113±27ms with a change in QRS width of -15±39ms (+72; -92ms). The mean his-bundle sensing was 5,38±5,6mV and the mean threshold 1,1±0,86V over 1,0±0,5ms (0,4;1,5ms). The proportion of ventricular pacing was 75±36%. Conclusion Electroanatomic-guided His bundle pacing as a new innovative technic for physiological pacing is viable including high implantation success rate as well as electric impact, both regarding QRS width and pacing threshold.

Numerous processes, including heat shock, inflammatory and tissue regeneration responses are activated upon a burn injury, resulting in a complex pathophysiology affecting the whole organism. Reliable burn models are needed to elucidate the exact sequence of events during the healing process and to evaluate the effects of innovative wound dressings. We analysed contact burns induced on fresh skin explants. Gene expression patterns and cytokine production profiles of key mediators of the local heat shock response, inflammation, and of tissue regeneration were analysed for up to 24 hours after the burn injury. We also used the open flow microperfusion (OFM) technology to analyze mediators released to the interstitial fluid (ISF). Significant alterations in gene expression were found for heat shock, inflammatory and tissue repair responses as soon as one hour after burn injury. In the ISF also significant changes were found for a number of mediators, such as VEGFA. Cooling the injuries using bacterial nanocellulose dressings reduced the thermal damage significantly. This novel ex vivo human skin approach is suitable to study especially the immediate early responses to skin injuries including burns. Gene expression patterns, cytokine profiles, histology and ultrastructural analyses give valuable insights into the mechanisms at the very beginning of the wound healing process. This model can be used to evaluate innovative wound dressings as shown for a bacterial nanocellulose dressing.

This study describes the quantification of the inflammation parameters cytokines and eicosanoids in dermal interstitial fluid (dISF) samples during the process of wound healing. The dISF samples were collected with the minimally invasive sampling method open flow microperfusion (OFM) and split skin wounds were induced in farm pigs at a depth of 0.6 mm. The cytokine and eicosanoid concentrations were monitored in six and two days old wounds and compared to fresh wounds (directly after wounding) and to control sites (non-wounded skin). Two OFM probes were inserted in the wound edges and two OFM probes on the wound ground of each wound. Diluted dISF samples were collected with OFM over a period of six hours in two sequential sampling intervals, each lasting for three hours. For the measurement of the porcine cytokines a multiplexing platform using the MSD system was established, and the eicosanoids were quantified using liquid chromatography mass spectrometry. We successfully assessed the levels of commonly monitored cytokines together with eicosanoids during the wound healing process. Cytokine as well as eicosanoid concentrations in the wound ground were higher in two and six day old wounds than in fresh wounds or in the control sites. The measured cytokine and eicosanoid concentrations were lower in samples taken from wound edges than those taken from wound grounds. Furthermore, the cytokine and eicosanoid concentrations found in samples collected in the first OFM sampling interval were higher than those found in samples collected in the second interval. The obtained results showed that the combination of tissue-specific sampling using OFM and quantitative measurements of the inflammatory markers cytokines and eicosanoids creates new avenues for a better understanding of the process of wound healing.