Klinikum Coburg

Abstract Background Electrocardiogram (ECG)-monitoring covering several days is recommended by current guidelines to detect atrial fibrillation (AF) and other arrhythmias in stroke patients. In clinical practice, the extent of rhythm monitoring varies. In this analysis, we use data from the 24-hour screening-Holter-ECGs of the ongoing randomized multicenter trial Find-AF 2 to assess the detection rate of AF and other sustained arrhythmias. Methods and Results Find-AF 2 (NCT04371055) is a randomized, controlled, open-label, parallel arm, multicenter trial with central AF adjudication (intervention arm) and blinded endpoint assessment [1]. Patients ≥60 years with recent (≤30 days) ischemic strokes according to the AHA/ASA definition of any etiology are screened for eligibility. All eligible patients received a 24-hour Holter-ECG prior to randomization which was reviewed by the ECG core lab following a predefined standard operation procedure. The primary analysis focused on the detection of AF ≥30 seconds and the extent of excessive supraventricular ectopic activity. Bradycardic arrhythmias were deemed relevant if they led to pauses >2.5s or if the heart rate <40 bpm was accompanied by higher-degree AV-blocks. Tachycardic arrhythmias were reported if they persisted ≥ 30 seconds, had a mean rate of >120 bpm or had a ventricular origin. A total of 5411 Screening-Holter-ECGs from 51 study centers were analyzed. The mean age was 72.4±7.6 years and 2194 (41%) patients were female. Holter ECGs were performed after a median [IQR] of 3 [2; 5] days post stroke. We found sustained arrhythmias or pauses in 176 patients (3.3%). AF was seen in 78 patients (1.4%) with a median [IQR] burden of 51% [19; 95] and a median [IQR] duration of the longest episode of 690 [240;1170] minutes (Figure 1). Oral anticoagulation was initiated in all patients with AF. In 72 patients (1.3%), pauses > 2.5 s were seen with a mean duration of the longest pause of 3.3±0.9 s and the longest pause lasting for 7.1 s. Seventeen pauses and two bradycardic episodes occurred due to higher-degree AV-blocks, 41 due to sinus node arrest or sino-atrial block and fourteen during AF. One patient received a pacemaker. We observed regular supraventricular tachycardias in 39 patients (0.7%) and one ventricular tachycardia (0.02%). Conclusion Overall, 3.2 % of ischemic stroke patients had relevant arrhythmias, with an AF detection rate of 1.4%. Potentially life-threatening arrhythmias were rare, and the number needed to screen for a change in therapy was 69. Figure 1: Distribution of relevant arrhythmias. SVT=Supraventricular tachycardia. Figure 2: The empirical cumulative distribution is shown for the duration of the longest AF episode. AF= Atrial Fibrillation. Figure 1 Figure 2

Abstract Background and Aims The mechanisms driving the development of extracapillary lesions in crescentic glomerulonephritis (CGN) and focal segmental glomerulosclerosis (FSGS) remain poorly understood. This study investigates the role of serotonin (5-HT) and its receptors, specifically HTR2A and HTR2B, in murine models of these diseases. Method This study employed a combination of genetic, pharmacological, and in vitro approaches to elucidate the role of serotonin receptors in CGN and FSGS. Results We found that both receptors were upregulated in glomerular parietal epithelial cells in both human and murine CGN. We found that both genetic deletion and pharmacological inhibition of the 5-HT2A receptor effectively reduced glomerular crescents and sclerosis, while the compensatory upregulation of 5-HT2A receptors in response to 5-HT2B receptor deficiency or antagonism underscores a complex interplay between these receptor subtypes. Bone marrow-specific deletion and repletion of HTR2A-competent cells did not alter the course of experimental CGN, suggesting that the 2A signals driving CGN originate from the kidney. The Alport model, which is primarily degenerative, also benefitted in a similar way from 2A deletion, further corroborating the role of kidney resident 2A signaling in these diseases. Additionally, platelets were identified as a source of 5-HT and a crucial upstream factor in promoting PEC activation and exacerbating the disease, with their depletion leading to significant mitigation of disease severity. Finally, in vitro studies using murine PECs indicated the pivotal role of 5-HT signaling in PEC activation. Conclusion Our findings highlight a critical role of 5-HTR2A in PEC activation, proposing it as a new potential target for the treatment of glomerular kidney diseases.

Objectives: The relationship between oral health and general health of geriatric in-hospital patients (GIH) who are poly-morbid and edentulous is currently unclear. This study determined the relationship between oral health and general health, and further implications and recommendations were derived. Methods: This retrospective cohort study included 81 GIH patients with impairment of oral state and masticatory function and need for immediate prosthetic treatment. The number of medical diagnoses, particularly main diagnoses of being hospitalized, comorbid diagnoses and the dental/oral state, were evaluated. Laboratory data of vitamin D3 and albumin concentrations were measured. Intraoral risk factors (IRF) affecting the masticatory function were intraoral inflammation, mucogingival impairment (MGI) and severe bone crest atrophy (SBCA). Masticatory function was evaluated by DMF*-T Index (number of destroyed/diseased, missing teeth and artificial fabrication), Eichner Index and Scores. The clinical relevance was surveyed by significance and effect size calculations. Results: In GIH, the number of medical diagnoses correlated significantly with the occurrence of IRFs. SBCA was the most affecting IRF, as measured by Eichner Index at baseline (p = 0.001). Single main diagnoses CNS and gastro-intestinal disease (GID) correlated with both deficiency of vitamin D3 levels (p = 0.011; p = 0.028) and hypoalbuminemia (p = 0.013; p = 0.023). Single comorbid diagnoses significantly correlated with both vitamin D3 deficiency and hypoalbuminemia (CVD (p = 0.031); DM (p = 0.042). Hypoalbuminemia was further found to be correlated with the sum of comorbid diagnoses (p = 0.033). Conclusions: GIH patients suffered from general and dental poly-morbidity. The prevalence of diseases was higher due to SBCA and impaired masticatory function. Deficiency of vitamin D3 and hypoalbuminemia were possible malnutrition markers.

Rectal cancer disproportionately affects the elderly population, with more than half of cases diagnosed in individuals aged 70years or older. Frail patients in this group often face significant challenges tolerating the standard treatment of total mesorectal excision (TME), due to elevated risks of surgical complications and perioperative morbidity. Advances in radiotherapy techniques offer a viable alternative, providing effective tumor control while minimizing treatment-related toxicity. Recent clinical trials, including OPERA and MORPEUS, have demonstrated that dose-escalated radiotherapy, which integrates external beam (chemo)radiotherapy (EBRT) with high-dose-rate endorectal brachytherapy (HDR-BT) or contact X-ray brachytherapy (CXB), can achieve high clinical response rates and facilitate organ preservation in younger, healthier patient cohorts. Building on these findings, the ACO/ARO/AIO-22 study seeks to adapt these innovative approaches to meet the needs of elderly and frail patients with rectal cancer. The ACO/ARO/AIO-22 trial is a prospective multicentre controlled trial. Elderly (age ≥70years) and/or frail patients with non-metastatic rectal adenocarcinoma (cT1-3d N0/+ M0, mrCRM - / +) localized 0-16cm from the ano-cutaneous line, unable to undergo radical surgery can be included. The initial treatment comprises an external beam radiation (EBRT) regime with 13×3Gy (total: 39Gy) over a period of two and a half weeks. Following initial restaging 6.5weeks after completion of EBRT, endorectal HDR-BT will be delivered with 3 weekly fractions of 8Gy to a total dose of 24Gy (prescribed at the radial margin of the tumor; with a maximum prescription depth of 10mm); alternatively, with CXB with 90Gy in 3 weekly fractions. The primary objective is complete or near complete clinical response (cCR or ncCR) and the second primary endpoint is quality of life (QoL) measured with the EORTC QLQ-ELD14, both at 12months after treatment start. The ACO/ARO/AIO-22 prospective multicentre trial will evaluate organ preservation rates and QoL after combining EBRT with endorectal HDR-BT in elderly and/or frail patients with rectal cancer.Trial Registration:Clinicialtrials.gov number: NCT06729645.

BackgroundPulmonary vein isolation (PVI) is the cornerstone therapy for symptomatic drug‐refractory atrial fibrillation yet is not curative in a large segment of patients. Focal and rotational drivers are proposed to be involved in atrial fibrillation mechanisms but their ablation has produced variable outcomes. REAFFIRM (The Randomized Evaluation of Atrial Fibrillation Treatment with Focal Impulse and Rotor Modulation Guided Procedures) trial (NCT‐02274857) objective was to compare the safety and effectiveness of conventional ablation with and without Focal Impulse and Rotor Modulated (FIRM) ablation, guided by global basket mapping, for the treatment of persistent atrial fibrillation.MethodsThree hundred seventy‐five patients were enrolled and randomized at 18 centers. The Intent‐to‐Treat population consisted of 350 patients (171 FIRM, 179 Conventional). Primary effectiveness was defined as single procedure freedom from atrial fibrillation/atrial tachycardia recurrence at 3 to 12 months post index procedure.ResultsThree hundred twenty‐four patients completed the 12‐month follow‐up. Patients in the FIRM arm had a larger left atrium (P <0.01). Primary effectiveness at 3 to 12 months was 69.3% in FIRM and 67.5% in Conventional (NS), with no difference in ablation procedure time or safety. A subset of patients (41% FIRM, 49% Conventional) received extra ablation. Primary effectiveness in the on‐treatment subgroups was 65% PVI‐only, 69.6% PVI +extra, 77.7% FIRM+ PVI‐only, and 57.7% FIRM+ PVI +extra (P=0.09).ConclusionsIntention‐to‐treat analysis failed to provide evidence for the superiority of adding ablation of focal or rotational sites to conventional ablation.RegistrationURL: https://clinicaltrials.gov; Unique Identifier: NCT‐02274857.

Background/IntroductionThe TAILORED-AF trial (NCT04702451) was the first randomized, superiority trial demonstrating that artificial intelligence (AI)-guided ablation of persistent atrial fibrillation (AF) patients targeting spatiotemporal dispersion in addition to pulmonary vein isolation (PVI) is superior to PVI alone after one year of follow-up.PurposeThis TAILORED-AF sub-analysis aims to characterize spatiotemporal dispersion regions in relation to atrial regions where AF terminated during an AI-guided tailored ablation procedure.MethodsSpatiotemporal dispersion maps were built during index ablation procedures with an artificial intelligence-guided spatiotemporal dispersion software. Dispersion atrial extent was defined as the ratio of dispersion surface area in a chamber over its total chamber surface area quantified with an in-house algorithm. The algorithm estimates pixel surface area values from 2D snapshots collected from 3D navigation maps. After (i) conversion of antero-posterior and postero-anterior 2D view snapshots into grayscale-transformed images, (ii) the background was removed and the atria were segmented. Then, (iii) tags were detected, segmented and (iv) connected to remnant regions. Finally, spatiotemporal dispersion region locations and extent were superimposed with tags corresponding to AF termination locations in patients in whom AF was terminated. This corresponded to a location where AF terminated by ablation into sinus rhythm/atrial tachycardia or where the AF cycle length increased by a minimum of 20ms.ResultsThe Tailored arm population included 187 persistent and long-standing persistent AF patients. The dispersion extent was higher in the left atrium (LA) compared to the right atrium (RA) (14.7% [8.1%-24.5%] vs 0.6% [0.0%-2.5%], p<0.0001). All patients (100%) had dispersion in the LA, whereas dispersion was only detected in the RA in 79% of the patients. The most frequent regions in LA exhibiting dispersion were the LA posterior wall with 20% [8%-31%] extent, LA anterior wall with 15% [8%-25%] extent and the LA roof with 10% [4%-19%] extent.The acute AF termination rate was 66%. All AF termination locations (100%) were found within dispersion regions: 25% in the lower quartile dispersion extent, 26% in the medium quartile and 49% in the higher quartile. In 81% of the patients, AF termination occurred in the LA, from which 20% located in the PV region and 80% outside the PV region. AF terminated in the RA in 19% of the patients (Figure).Conclusion(s)While pursuing an AI-guided ablation of persistent atrial fibrillation, spatiotemporal dispersion and AF termination predominantly occurs in the left atrium. Still, 19% of termination is observed after ablation in minimally extended regions of the RA. These findings highlight the importance of mapping and ablating in the RA when conducting a spatiotemporal dispersion-based ablation.

Background: Catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure (HF) reduces mortality and hospitalizations and improves ejection fraction (EF). Arrhythmia-induced cardiomyopathy (AIC) is diagnosed after complete resolution of HF following AF ablation. Aim: We aim to identify the prevalence and pre-ablation predictors value of AIC among patients with persistent AF and HF enrolled in the DECAAF II trial. Methods: We utilized the DECAAF II database, where 815 patients with persistent AF underwent late-gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) before and three-months after receiving CA for AF. Patients were randomized to receive pulmonary vein isolation (PVI) in addition to substrate modification (SM) or standard PVI alone. Ejection fraction was collected before, and three months after CA. Patients were asked to submit a single-lead ECG every day or when feeling symptoms using a single-lead handheld ECG device. AF Burden was defined as the percentage of monitored time spent in AF. For this analysis, we only included patients diagnosed with HF with available LV function data before and after CA. We defined AIC as HF and AF patients who experience EF improvement to ≥50% after ablation, with at least 10% improvement in EF. Results: We identified 119 patients with HF and persistent AF; 72 (60.5%) fulfilled criteria for AIC, and 47 (39.5%) were non-AIC patients[SC1] . At baseline, AIC patients had an LVEF of 39.1±7.9, non-AIC had 39.2±7.9 (p=0.9). There was no difference between the two groups in baseline characteristics, AF burden [SC2] or AF recurrence (Table). The distribution of fibrosis from LGE-CMR prior to ablation was the only significant pre-ablation predictor of AIC among patients with HF and persistent AF. Patients with AIC had significantly lower percentage of fibrosis in the septal wall compared with non-AIC patients (12.2±10 vs 20.7±11.4, p &lt;0.001), regardless of the total amount of LA fibrosis. Conclusion: In this post-hoc analysis of the DECAAF II trial, we found that up to 60% of patients with HF and persistent AF have AIC rather than primary cardiomyopathy. We also described LGE-MRI as a significant differentiator between AIC and other cardiomyopathies complicated with arrhythmia.

Abstract Background While pulmonary vein isolation (PVI) is the gold standard approach of treatment of atrial fibrillation (AF), the optimal strategy in case of AF recurrences for redo patients is not well established. Several studies described the usefulness of ablating in atrial regions exhibiting abnormal electrograms, i.e. spatio-temporal dispersion, during AF and an artificial intelligence (AI) electrograms (EGMs)-based software solution has been developed and validated to obtain real-time adjudications of multipolar electrograms in de novo patients. Purpose This study sought to evaluate the novel AI-EGMs-based software approach for redo-AF ablation procedures. Methods This study was a retrospective, multicentric, nonrandomized study. Patients with recurrent symptomatic AF were enrolled in 7 European centers. Redo ablation procedures were performed using the AI software and acute and long-term outcomes after ablation were evaluated. Results A total of 117 patients with refractory symptomatic AF admitted for redo procedure were included with 30% paroxysmal, 42% short-standing persistent and 28% long-standing persistent AF at the time of the redo procedure. During the index procedures, a previous PVI ablation was performed in all patients while additional ablation such as lines and EGM-based ablation was performed in 64 patients (55%). Out of 117 patients, 30 (26%) presented with structural heart disease, 61 (52%) with hypertension, 31 (26%) with a BMI &amp;gt;30, 16 (14%) a sleep apnea syndrome and 24 (20%) had an antiarrhythmic treatment at the time of the procedure. The average AF history was 6.54 ± 4.15 years with an average sustained duration equal to 25 ± 62 months. AI-EGMs-based AF ablation was performed in all patients and easily integrated in the physicians’ workflow during redo procedures. AF termination, i.e. AF regularization or sinus rhythm conversion, occurred in 82/117 patients (71%) with sinus rhythm conversion by ablation in 79/117 patients (68%). After a mean follow-up of 11 ± 5 months, 81% of patients were free from documented AF, with or without antiarrhythmic drugs (AADs) after one redo procedure and 60% of patients were free from any documented atrial arrhythmia, with or without AADs, after one redo procedure per patient. Furthermore, we observed that 77%, 84% and 82% of patients were free from documented AF with or without AADs in paroxysmal, short-standing and long-standing persistent AF patients respectively, and that 71%, 59% and 49% of patients were free from any documented atrial arrhythmia with or without AADs in paroxysmal, short-standing and long-standing persistent AF patients respectively. Conclusions This retrospective study reports that patient-tailored spatiotemporal dispersion ablation is a relevant and standardized approach for repeat AF ablation. This was obtained with an AI-EGMs-based software solution, which may be added to the operative workflow of redo AF procedures.

Abstract Background Dual-chamber (DC) cardiac pacing is thought to offer a clinical benefit as compared to single-chamber (SC) cardiac pacing. With the introduction of leadless pacers and the recommendation for DC-pacing in sinus node dysfunction, the implantation rates of SC-pacemaker have markedly decreased. However, little is known from real word national healthcare data. The purpose of this VIDEO substudy is to analyze the German national healthcare situation with regards to SC- vs. DC-pacing. Methods German hospitals are obliged to provide a dataset including case data, diagnosis, operational and procedural codes to the Institute for hospital remuneration system (InEK) every year. The VIDEO project aims at analyzing these data to report real world data on patients undergoing Cardiac implantable electronic device (CIED) surgery in Germany. As of now, 22 German centers were contacted by the Institute for Myocardial Infarction Research (IHF). Ten centers provided their data from 2018 to 2023. Datasets from the remaining centers are pending. The project is supported by the German Heart Foundation. Results A total of 12,474 patients (35.6% females, mean age 71.2 ± 14.5 years) underwent CIED surgery at 10 centers in Germany. A SC-pacemaker was implanted in 1071 patients (group A), a DC-pacemaker in 6343 patients (group B) and other CIEDs including defibrillators in the remaining 5060 patients. Only a minority of the surgeries in both groups were revisions. The median patient age in group A was 81 years (IQR 77;85) compared to 78 years (IQR 70;83) in group B. Of the patients receiving a SC-pacemaker only 4.2% were adults between 40-64 years old compared to 13.4% in the DC-pacemaker group. Diabetes mellitus, chronic obstructive pulmonary disease and a heart failure were more common in group A (30.5% vs. 25.1%, 9.0 vs. 6.0%, 53.2% vs. 35.9%, p &amp;lt;0.01). Atrial fibrillation was known in 942/1050 (89.7%) in patients receiving as SC-pacemaker and in 2589/6197 (42.4%) in those with a DC-pacemaker (p &amp;lt; 0.01). The main indication for pacemaker implantation in both groups was atrioventricular block (41.5% vs. 69.5%, p &amp;lt;0.01) followed by sinus node dysfunction (19.7% vs 27.6%, p &amp;lt; 0.01). All patients were treated as inpatients. The median hospital stay in group A was significantly longer than in group B (8.0 (IQR 3.0; 16.0) vs. 6.0 (IQR 2.0; 13.0), p &amp;lt; 0.01). Half of the patients in both groups were treated on an intensive care unit (ICU) (51.7% and 56.6%) with a median ICU stay of 2.8 (IQR 1.1;5.8) in group A and 2.3 (IQR 1.0;10.0) in Group B. The in-hospital mortality was higher in patients receiving a SC-pacemaker (2.6%) as compared to the DC-pacemaker group (1.6%). Conclusion In Germany, single-chamber pacemakers are implanted six times less common than dual-chamber pacemakers. Patients receiving SC-pacemakers are older, more likely to suffer from permanent atrial fibrillation and have a prolonged in-hospital stay.