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For more than two decades the left ventricular ejection fraction (LVEF) has been utilized with practically uncritical absolutism for the risk stratification of patients with ischemic and, historically, also nonischemic cardiomyopathy, in order to identify patients who could be threatened by sudden cardiac death. Based on historical data and in the absence of other better predictive parameters, the LVEF continues to appear in the guidelines unchanged, with cut-off values that lie in the region of the measurement accuracy of LVEF as determined by echocardiography. The basic identification of high-risk patients who then really benefit from an implantable cardioverter defibrillator (ICD) must be re-evaluated under the aspect of a meaningfully altered interventional and pharmaceutical treatment of heart failure., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: C. Butter und G. Hindricks geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Importance: Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints., Objective: To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed., Design, Setting, and Participants: The SOLVE-CRT study was a prospective multicenter trial enrolling January 2018 through July 2022, with follow-up at 6 months. Data were analyzed from January 17, 2018, through February 15, 2023. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm., Interventions: Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery., Main Outcomes and Measures: The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV)., Results: The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, -21.0% to -11.7%) reduction in mean LVESV (P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications (P < .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%)., Conclusions and Relevance: The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations., Trial Registration: ClinicalTrials.gov Identifier: NCT0292203.

Background: Due to modern therapies, survival in metastatic renal cell carcinoma (mRCC) has been significantly prolonged. Nevertheless, patients suffering from advanced disease often present with severe symptoms. Early integration of palliative care into anti-cancer treatment has been shown to improve quality of life and may even prolong survival. Therefore, it is recommended to offer palliative care to patients with complex symptoms at the beginning of an advanced disease stage. To our knowledge, so far, no study has been conducted to examine the role of palliative care in patients with mRCC., Objectives: This study aimed to assess the symptom burden and quality of life before and after an inpatient palliative care treatment., Design: The study design is a retrospective observational study., Methods: We included patients with mRCC, who were admitted to our palliative care unit between 2011 and 2017 due to severe symptoms. The symptom burden was assessed at admission, throughout treatment, and at discharge. The evaluation consisted of the palliative care base assessment and daily documentation of relevant symptoms., Results: We evaluated 110 hospitalizations of 58 RCC patients. On average, patients were admitted to the palliative care unit 7 years after initial diagnosis (range 1-305 months). The median age was 70.5 years, 69% of the patients were male, 3% female. The main causes for admission were pain (52%) and dyspnea (26%), and the most frequent patient-reported symptoms were fatigue/exhaustion (87%), weakness (83%), and need for assistance with activities of daily living (83%). Multidisciplinary palliative care treatment led to a significant reduction in the median minimal documentation system (MIDOS) symptom score (15.6-9.9, p  < 0.001), the median numeric pain rating scale (3-0, p  < 0.001), and a significant reduction in mean ratings of the distress thermometer (5.5-3.1, p  = 0.016)., Conclusion: Our analysis shows that the integration of palliative care treatment is effective throughout the disease in mRCC and could measurably reduce the symptom burden in our patient population. Palliative care should not be equated with end-of-life care but should rather be integrated throughout advanced disease, particularly as soon as a cure is impossible., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Objectives: EF is a rare disease characterized by fibrosis and inflammation of the fascia, scleroderma-like skin indurations and optional blood eosinophilia. We aimed to expand the knowledge about its aetiology and pathogenesis., Methods: Biopsy specimens from 16 EF patients were assessed by histology, immunohistochemistry and quantitative reverse transcription PCR in comparison with anti-Mi-2+ DM patients and non-disease controls., Results: Histologically, EF shows mild to severe inflammation at the muscle-fascia interface, with frequent involvement of the underlying muscle tissue, though varying in degree. CD206+ macrophages predominate and eosinophils are detected within the fascia in the majority of cases, however in quite small numbers, and seen infrequently within the muscle. Activators of the so-called Th2-M2 pathway like STAT6 and IL-4 are upregulated leading to high expression levels of CD206. Activators of the so-called Th1-M1 pathway like STAT1 and IFN-γ (IFNG) are also upregulated, though not translating into a significant upregulation of the effector molecule COX2. Interestingly, activators or chemoattractants of eosinophils show no significant upregulation in EF compared with DM. EF shows features of perifascicular pathology comparable to DM, with upregulation of MHC class I and II; however, this is not accompanied by perifascicular atrophy or any signs of a type I IFN response or hypoxia-mediated processes., Conclusions: Our findings highlight a specific immune phenotype of leucocyte infiltrates in EF along features of perifascicular pathology similar to DM, while there is no evidence of hypoxia-mediated or type I IFN-associated processes with perifascicular fibre atrophy, indicating different pathomechanisms of muscle involvement., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: In a post hoc analysis of the VEST III trial, we investigated the effect of the harvesting technique on saphenous vein graft (SVG) patency and disease progression after coronary artery bypass grafting., Methods: Angiographic outcomes were assessed in 183 patients undergoing open (126 patients, 252 SVG) or endoscopic harvesting (57 patients, 114 SVG). Overall SVG patency was assessed by computed tomography angiography at 6 months and by coronary angiography at 2 years. Fitzgibbon patency (FP I, II and III) and intimal hyperplasia (IH) in a patient subset were assessed by coronary angiography and intravascular ultrasound, respectively, at 2 years., Results: Baseline characteristics were similar between patients who underwent open and those who underwent endoscopic harvesting. Open compared with endoscopic harvesting was associated with higher overall SVG patency rates at 6 months (92.9% vs 80.4%, P = 0.04) and 2 years (90.8% vs 73.9%, P = 0.01), improved FP I, II and III rates (65.2% vs 49.2%; 25.3% vs 45.9%, and 9.5% vs 4.9%, respectively; odds ratio 2.81, P = 0.09) and reduced IH area (-31.8%; P = 0.04) and thickness (-28.9%; P = 0.04). External stenting was associated with improved FP I, II and III rates (odds ratio 2.84, P = 0.01), reduced IH area (-19.5%; P < 0.001) and thickness (-25.0%; P < 0.001) in the open-harvest group and reduced IH area (-12.7%; P = 0.01) and thickness (-9.5%; P = 0.21) in the endoscopic-harvest group., Conclusions: A post-hoc analysis of the VEST III trial showed that open harvesting is associated with improved overall SVG patency and reduced IH. External stenting reduces SVG disease progression, particularly with open harvesting., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Chills and signs of systemic infection caused a patient's hospitalization. Reason for his productive cough and hemoptysis was apparently lobar pneumonia-until an unexpected result of blood cultures rendered further diagnostics necessary in this pacemaker patient., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: The aim of this study was to evaluate resuscitation skills, defined as recognition of resuscitation situations and performance of Basic Life Support (BLS) in students at the Brandenburg Model Medical School (BMM). Methods: Participating students (n=102) were randomized to different simulation scenarios: unconscious person with physiological breathing (15/min), gasping (<10/min) and apnea (resuscitation dummy AmbuMan ® Wireless with electronic recording). Primary endpoint was the proportion of students with correct decision for or against resuscitation. Secondary endpoint was resuscitation quality, self-assessment, and prior resuscitation experience. The latter two were assessed by questionnaire prior to the simulated situation. Results: Overall, there was a high risk for incorrectly omitted or incorrectly performed resuscitation (OR 3.4 [95% CI 1.4-8.1] p=0.005. The highest probability of error occurred in the unconsciousness and gasping groups. 22.3% of all performed resuscitations where at the same time indicated and reached the European Resuscitation Council recommendations for compression frequency, pressure depth and where as well = 90% relieved. A particularly large discrepancy emerged between participants' self-assessment of being prepared for a resuscitation situation by medical school and their actual documented resuscitation competence. Conclusion: The present data indicate significant uncertainty among students in recognizing a resuscitation situation. Even in curricula with a high proportion of practice and a high degree of students with completed vocational training in health care, resuscitation competence is poor., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Bülow et al.)

Objective: Epigenetic modifications are dynamic and influence cellular disease activity. The aim of this study was to investigate global DNA methylation in peripheral blood mononuclear cells (PBMCs) of RA patients to clarify whether global DNA methylation pattern testing might be useful in monitoring disease activity as well as the response to therapeutics., Methods: Flow cytometric measurement of 5-methyl-cytosine (5'-mC) was established using the cell line U937. In the subsequent prospective study, 62 blood samples were investigated, including 17 healthy donors and 45 RA patients at baseline and after 3 months of treatment with methotrexate, the IL-6 receptor inhibitor sarilumab, and Janus kinase inhibitors. Methylation status was assessed with an anti-5'-mC antibody and analysed in PBMCs and CD4+, CD8+, CD14+ and CD19+ subsets. Signal intensities of 5'-mC were correlated with 28-joint DASs with ESR and CRP (DAS28-ESR and DAS28-CRP)., Results: Compared with healthy individuals, PBMCs of RA patients showed a significant global DNA hypomethylation. Signal intensities of 5'-mC correlated with transcription levels of DNMT1, DNMT3B and MTR genes involved in methylation processes. Using flow cytometry, significant good correlations and linear regression values were achieved in RA patients between global methylation levels and DAS28-ESR values for PBMCs (r = -0.55, P = 0.002), lymphocytes (r = -0.57, P = 0.001), CD4+ (r = -0.57, P = 0.001), CD8+ (r = -0.54, P = 0.001), CD14+ (r = -0.49, P = 0.008) and CD19+ (r = -0.52, P = 0.004) cells., Conclusions: The degree of global DNA methylation was found to be associated with disease activity. Based on this novel approach, the degree of global methylation is a promising biomarker for therapy monitoring and the prediction of therapy outcome in inflammatory diseases., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Functional tricuspid regurgitation (TR) is a frequent finding in echocardiography. Literature suggests significant TR is associated with poor prognosis. Still, data remain limited. This study aimed to evaluate long-term prognostic implications in patients with TR., Methods: In this observational cohort study, data from 1650 consecutive patients were analysed. Primary endpoint was all-cause mortality. Mean follow-up time was 1090 days. TR grades at baseline and follow-up were compared. Survival analyses were performed to identify prognostic factors., Results: At baseline, 14.1% patients showed no, 63.8% mild, 17.4% moderate and 4.7% severe TR. 359 patients (21.8%) died within the study period. TR at baseline was associated with excess mortality. Moderate and severe TR were of prognostic implication in all subgroups irrespective of systolic pulmonary artery pressure (sPAP) (

Background: Biventricular endocardial pacing (BiV ENDO) is a therapy for heart failure patients who cannot receive transvenous epicardial cardiac resynchronization therapy (CRT) or have not responded adequately to CRT. BiV ENDO CRT can be delivered by a new wireless LV ENDO pacing system (WiSE-CRT system; EBR Systems, Sunnyvale, CA), without the requirement for lifelong anticoagulation., Objective: The purpose of this study was to assess the safety and efficacy of the WiSE-CRT system during real-world clinical use in an international registry., Methods: Data were prospectively collected from 14 centers implanting the WiSE-CRT system as part of the WiCS-LV Post Market Surveillance Registry. (ClinicalTrials.gov Identifier: NCT02610673)., Results: Ninety patients from 14 European centers underwent implantation with the WiSE-CRT system. Patients were predominantly male, age 68.2 ± 10.5 years, left ventricular ejection fraction 30.6% ± 8.9%, mean QRS duration 180.7 ± 27.0 ms, and 40% with ischemic etiology. Successful implantation and delivery of BiV ENDO pacing was achieved in 94.4% of patients. Acute (<24 hours), 1- to 30-day, and 1- to 6-month complications rates were 4.4%, 18.8%, and 6.7%, respectively. Five deaths (5.6%) occurred within 6 months (3 procedure related). Seventy percent of patients had improvement in heart failure symptoms., Conclusion: BiV ENDO pacing with the WiSE-CRT system seems to be technically feasible, with a high success rate. Three procedural deaths occurred during the study. Procedural complications mandate adequate operator training and implantation at centers with immediately available cardiothoracic and vascular surgical support., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

Patients, scientists and healthcare providers are increasingly interested in identifying interventions that not only reduce mortality but also improve symptoms, function and health-related quality of life. Health-related quality of life is a strong, independent predictor of mortality, cardiovascular events, hospitalization and treatment costs in patients with cardiac diseases. Remote monitoring of pacemakers has a positive effect on health-related quality of life and functional capacity and is equivalent to monitoring these patients in hospitals. Implantation of an implantable cardioverter defibrillator has a major impact on mental health, with the majority of patients experiencing the fear of ICD shocks as particularly detrimental to the quality of life. Variables, such as age, gender and duration of implantation should be considered in the assessment and planning of strategies for improving the quality of life of patients with electronic implantable cardiac devices.

Background: Delayed diagnosis and undertherapy of acute-on-chronic kidney injury (AKI-on-CKD) may trigger multiple organ injury and worsen clinical outcome., Objectives: This study focused on description of in-hospital care and cross-sectoral information transmission of patients with AKI-on-CKD including subgroup analyses (under surgical vs. non-surgical and nephrology vs. non-nephrology care)., Materials and Methods: At a university clinic, we analysed clinical measures and documentation in patients with AKI-on-CKD. Cox regression was performed to identify independent risk factors for in-hospital-mortality and 180-day mortality., Results: In 38 (25.3%) of 150 patients, progressing AKI-on-CKD was found. Nineteen patients (12.7%) received acute dialysis. Thirty patients (20.0%) died in hospital. Systemic hypotension (n = 76, 50.7%) and nephrotoxins (n = 26, 17.3%), both considered as causes for AKI-on-CKD, were treated in 36.8 and 19.2%, respectively, of affected patients. Fluid balance was documented in one third of patients. Nephrology referral was requested in 38 (25.3%) of patients (median 24.0 h after AKI-on-CKD start). Acute renal complications (n = 74, 49.3%) were an independent risk factor for in-hospital mortality (ExpB 6.5, p = 0.022) or 180-day mortality (ExpB 3.3, p = 0.034). Rarely, outpatient physicians were informed about AKI-on-CKD (n = 42, 28.0%) or renal function follow-up was recommended (n = 14, 11.7% of surviving patients)., Conclusions: Care gaps in therapy and cross-sectoral information transmission in patients with AKI-on-CKD were identified.

Objectives: Monoclonal antibodies are important in the treatment of rheumatoid arthritis (RA). This is the first trial to monitor the effect of adalimumab dose escalation in persistently active RA. The aim of this study was to identify the response to adalimumab to improve the basis for making decision in relation to actual drug capacity in serum., Methods: The disease activity of RA patients was assessed with CDAI and DAS28 before administration of additional 40 mg adalimumab one week after standard injection. Serum samples were analysed using the recoveryELISA technology, a combination of sandwich ELISA and competitive assay. The recoveryELISA measure the concentrations of free TNF-α, drug level, and the remaining active adalimumab in the patients' sera. An adalimumab concentration of 5.0-10.0 g/mL was defined as the targeted therapeutic window., Results: Five of 8 patients achieved moderate EULAR response by dose escalation. The results of the free adalimumab and TNF-α neutralisation measurements allowed a separation of the cohort (n=17) into three groups. Group 1 represents 18% of the patients with free adalimumab level higher 30.0 μg/mL and TNF-α neutralisation above 95%. Group 2 (47%) consists of patients within the therapeutic window with balanced free adalimumab and TNF-α neutralisation values. Group 3 contains 35% of the cohort with low concentrations of free adalimumab and lowest remaining TNF-α-neutralisation capacity. Anti-drug antibodies were detected in four patients but did not prevent response to treatment., Conclusions: Drug and antigen monitoring using recoveryELISA may support dose decision to avoid unnecessary switch in medication or possible overtreatment.

Background: Inflammatory rheumatic diseases and their treatment cause various renal manifestations requiring modification of treatment., Objectives: Discussion of renal manifestations in selected rheumatic diseases, including their impact on general prognosis and therapy., Materials and Methods: Basic literature and expert opinions are analyzed and discussed., Results: Inflammatory rheumatic diseases and their treatment cause various renal manifestations, including glomerular, tubular, interstitial, and vascular damage. The type of damage determines both, associated clinical symptoms (i.e. hematuria, proteinuria, loss of kidney function) and the renal and overall survival as will be discussed here for rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjögrens syndrome, cryoglobulinemia and ANCA-associated vasculitis., Conclusion: Renal manifestations are generally indicators of high disease activity and usually require more intensive treatment of the underlying rheumatic disease. Early and rigorous treatment, which has to be adapted to renal function, is capable of improving renal and overall survival in many of the affected patients.