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Activation of the CXCL12/CXCR4/ACKR3 axis is known to aid myocardial repair through ischemia-triggered hypoxia-inducible factor-1α (HIF-1α). To enhance the upregulation of HIF-1α, we administered roxadustat, a novel prolyl hydroxylase inhibitor (PHI) clinically approved by the European Medicines Agency 2021 for the treatment of renal anemia, with the purpose of improving LV function and attenuating ischemic cardiomyopathy. Methods: We evaluated roxadustat's impact on HIF-1 stimulation, cardiac remodeling, and function after MI. Therefore, we analyzed nuclear HIF-1 expression, the mRNA and protein expression of key HIF-1 target genes (RT-PCR, Western blot), inflammatory cell infiltration (immunohistochemistry), and apoptosis (TUNEL staining) 7 days after MI. Additionally, we performed echocardiography in male and female C57BL/6 mice 28 days post-MI. Results: We found a substantial increase in nuclear HIF-1, associated with an upregulation of HIF-1α target genes like CXCL12/CXCR4/ACKR3 at the mRNA and protein levels. Roxadustat increased the proportion of myocardial reparative M2 CD206+ cells, suggesting beneficial alterations in immune cell migration and a trend towards reduced apoptosis. Echocardiography showed that roxadustat treatment significantly preserved ejection fraction and attenuated subsequent ventricular dilatation, thereby reducing adverse remodeling. Conclusions: Our findings suggest that roxadustat is a promising clinically approved treatment option to preserve myocardial function by attenuating adverse remodeling. [ABSTRACT FROM AUTHOR]

Immune activation coincides with disturbances in iron and vitamin D metabolism in patients with cardiomyopathy. In this study, we investigated whether there are differences regarding immune activation, iron and vitamin D metabolism between the different cardiomyopathy aetiologies.

The burgeoning domain of telehealth has witnessed substantial transformation through the advent of advanced technologies such as Large Language Models (LLMs). This study examines the integration of LLMs in heart failure management, with a focus on HerzMobil as a pioneering telehealth program. The technical underpinnings of LLMs, their current applications in the medical field, and their potential to enhance telehealth services, have been explored. The paper highlights the benefits of LLMs in patient interaction, clinical documentation, and decision-making processes. Through the HerzMobil case study, improvements in patient self-management and reductions in hospital readmission rates have been observed, showcasing the successful application of telehealth in chronic disease management. The paper also delves into the challenges and ethical considerations of LLM integration, such as data privacy, potential biases, and regulatory compliance, underscoring the need for a balanced approach that prioritizes patient safety and ethical standards. [ABSTRACT FROM AUTHOR]

Aim: The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF). Methods and results: In this prospective multicentre, double‐blind, two‐armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12 weeks. All patients had left ventricular ejection fraction (LVEF) ≤30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 μg/kg/min every 2 weeks, or as 24 h infusion at a rate of 0.1 μg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26 weeks, respectively. Due to the COVID‐19 pandemic, the planned number of patients could not be recruited. The final modified intention‐to‐treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p = 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14 weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12–7.68; p = 0.021) and 26 weeks (HR 1.64, 95% CI 0.87–3.11; p = 0.122). Conclusions: Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post‐hospitalization clinical stability. [ABSTRACT FROM AUTHOR]

Heart failure is a common chronic disease which is associated with high re-hospitalization and mortality rates. Within the telemedicine-assisted transitional care disease management program HerzMobil, monitoring data such as daily measured vital parameters and various other heart failure related data are collected in a structured way. Additionally, involved healthcare professionals communicate with one another via the system using free-text clinical notes. Since manual annotation of such notes is too time-consuming for routine care applications, an automated analysis process is needed. In the present study, we established a ground truth classification of 636 randomly selected clinical notes from HerzMobil based on annotations of 9 experts with different professional background (2 physicians, 4 nurses, and 3 engineers). We analyzed the influence of the professional background on the inter annotator reliability and compared the results with the accuracy of an automated classification algorithm. We found significant differences depending on the profession and on the category. These results indicate that different professional backgrounds should be considered when selecting annotators in such scenarios. [ABSTRACT FROM AUTHOR]

Background: The daily increasing amount of health data from different sources like electronic medical records and telehealth systems go hand in hand with the ongoing development of novel digital and data-driven analytics. Unifying this in a privacy-preserving data aggregation infrastructure can enable services for clinical decision support in personalized patient therapy. Objectives: The goal of this work was to consider such an infrastructure, implemented in a smart registry for heart failure, as a comparative method for the analysis of health data. Methods: We analyzed to what extent the dataset of a study on the telehealth program HerzMobil Tirol (HMT) can be reproduced with the data from the smart registry. Results: A table with 96 variables for 251 patients of the HMT publication could theoretically be replicated from the smart registry for 248 patients with 80 variables. The smart registry contained the tables to reproduce a large part of the information, especially the core statements of the HMT publication. Conclusion: Our results show how such an infrastructure can enable efficient analysis of health data, and thus take a further step towards personalized health care. [ABSTRACT FROM AUTHOR]

We aimed to ascertain the real-world diagnostic accuracy of bone scintigraphy in combination with free light chain (FLC) assessment for transthyretin (ATTR) cardiac amyloidosis (CA) using the histopathological diagnosis derived from endomyocardial biopsy (EMB) as a reference standard. We retrospectively analyzed 102 patients (22% women) with suspected CA from seven Austrian amyloidosis referral centers. The inclusion criteria comprised the available results of bone scintigraphy, FLC assessment, and EMB with histopathological analysis. ATTR and AL were diagnosed in 60 and 21 patients (59%, 21%), respectively, and concomitant AL and ATTR was identified in one patient. The specificity and positive predictive value (PPV) of Perugini score ≥ 2 for ATTR CA were 95% and 96%. AL was diagnosed in three out of 31 patients (10%) who had evidence of monoclonal proteins and a Perugini score ≥ 2. When excluding all patients with detectable monoclonal proteins (n = 62) from analyses, the PPV of Perugini score ≥ 2 for ATTR CA was 100% and the NPV of Perugini score < 2 for ATTR CA was 79%. Conclusively, ATTR CA can be diagnosed non-invasively in the case of a Perugini score ≥ 2 and an unremarkable FLC assessment. However, tissue biopsy is mandatory in suspected CA in any other constellation of non-invasive diagnostic work-up. [ABSTRACT FROM AUTHOR]

Background: Clinical notes provide valuable data in telemonitoring systems for disease management. Such data must be converted into structured information to be effective in automated analysis. One way to achieve this is by classification (e.g. into categories). However, to conform with privacy regulations and concerns, text is usually de-identified. Objectives: This study investigated the effects of de-identification on classification. Methods: Two pseudonymisation and two classification algorithms were applied to clinical messages from a telehealth system. Divergence in classification compared to clear text classification was measured. Results: Overall, de-identification notably altered classification. The delicate classification algorithm was severely impacted, especially losses of sensitivity were noticeable. However, the simpler classification method was more robust and in combination with a more yielding pseudonymisation technique, had only a negligible impact on classification. Conclusion: The results indicate that deidentification can impact text classification and suggest, that considering deidentification during development of the classification methods could be beneficial. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure are at risk of perioperative complications with elective cardiac surgery. Objectives: Conception of a multidisciplinary telemedicine-assisted optimisation project for high-risk patients prior to elective cardiac surgery. Methods: Multidisciplinary concept design. Results: A pilot-project for 30 patients was developed. Conclusion: Design of the first preoperative telemonitoring-assisted optimisation project for high-risk patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Background Primary pericardial mesothelioma (PPM) is a rare form of highly aggressive cancer. Many patients are diagnosed only at an advanced stage. Therefore, the overall survival rate is poor with a median survival of 3 months. In some rare cases, the PPM infiltrates the myocardium causing lethal myocardial dysfunction. Case summary A 66-year-old patient was transferred to our centre with the provisional diagnose of pericarditis of unknown origin. Using extensive cardiac imaging [echocardiography, computed tomography (CT), positron emission tomography–CT, cardiac magnetic resonance imaging, left and right heart catheterization, coronary angiography], PPM was finally diagnosed. After consultation with the oncologists, the heart team decided to resect the tumour first due to impaired haemodynamics and then initiate adjuvant chemotherapy. Intraoperatively, myocardial infiltration of the tumour became apparent, which was not detected preoperatively despite intensive imaging. Complete resection of the PPM was not possible and effective decompression of the ventricle could not be achieved. The patient died on the first postoperative day. Discussion Surgical therapy is indicated in many forms of cardiac tumours. However, when a tumour invades the myocardium, surgery often comes to its limits. In this case, myocardial invasion of PPM could not be detected despite extensive imaging. We therefore suggest that possible myocardial infiltration by PPM, and thus potential limitations of cardiac surgery, should be considered independently of imaging results when therapeutic options are discussed. [ABSTRACT FROM AUTHOR]

Telehealth services for long-term monitoring of chronically ill patients are becoming more and more common, leading to huge amounts of data collected by patients and healthcare professionals each day. While most of these data are structured, some information, especially concerning the communication between the stakeholders, is typically stored as unstructured free-texts. This paper outlines the differences in analyzing free-texts from the heart failure telehealth network HerzMobil as compared to the diabetes telehealth network DiabMemory. A total of 3,739 free-text notes from HerzMobil and 228,109 notes from DiabMemory, both written in German, were analyzed. A pre-existing, regular expression based algorithm developed for heart failure free-texts was adapted to cover also the diabetes scenario. The resulting algorithm was validated with a subset of 200 notes that were annotated by three scientists, achieving an accuracy of 92.62%. When applying the algorithm to heart failure and diabetes texts, we found various similarities but also several differences concerning the content. As a consequence, specific requirements for the algorithm were identified. [ABSTRACT FROM AUTHOR]

Summary: The enormous progress made in recent years in the field of information and communication technology and also in sensor and computer technology has affected numerous fields of medicine and is capable of inducing even radical changes in diagnostic and therapeutic processes. This is particularly true for cardiology, where, for example, telemetric monitoring of cardiac and circulatory functions has been in use for many years. Nevertheless, broad application of newer telemedical processes has not yet been achieved to the extent one would expect from the encouraging results of numerous clinical studies in this field and the state of the art of the underlying technology. In the present paper, the Working Group on Rhythmology of the Austrian Cardiological Society aims to provoke a critical discussion of the digital change in cardiology and to make recommendations for the implementation of those telemedical processes that have been shown to exert positive effects on a wide variety of medical and economic parameters. The greatest benefit of telecardiological applications is certainly to be found in the long-term care of patients with chronic cardiovascular diseases. Accordingly, follow-up care of patients with cardiological rhythm implants, management of chronic heart failure and secondary prevention following an acute cardiac event during rehabilitation are currently the most important fields of application. Telemedicine is intended to enable high-quality and cost-efficient care for an increasing number of patients, whose care poses one of the greatest challenges to our healthcare system. Not least of all, telemedicine should make a decisive contribution to improving the quality of life of this segment of the population by favorably influencing mortality, morbidity and hospitalization as well as the patient's contribution to treatment. [ABSTRACT FROM AUTHOR]

Aims: Anaemia and iron deficiency (ID) are frequently found in patients with chronic heart failure (CHF) and associated with adverse outcome. However, it is unclear whether absolute [transferrin saturation (TSAT) <20%, ferritin <100 μg/L] or inflammation‐driven functional ID (TSAT <20%, ferritin >100 μg/L) with and without anaemia had similar or different consequences for such patients. Methods and results: Within this retrospective cohort study, 2223 patients (1601 men and 622 women) with CHF, referred to our department, between 2000 and 2018, were followed for a median time of 84 months. Anaemia was found in 393 patients and was an independent predictor for an adverse outcome [HR 2.164 (95% CI 1.865–2.512), P < 0.001]. In 674 patients with available parameters of iron metabolism, ID was present in 228 patients and was associated with an unfavourable outcome [HR 1.499 (95% CI 1.158–1.940), P = 0.002]. ID was best predicting an adverse outcome in men ≤59 years, with heart failure with reduced ejection fraction, preserved kidney function, no inflammation, and a body mass index (BMI) ≥25.5 kg/m2. Functional ID in women and absolute ID in men were associated with poor prognosis. Of note, TSAT <20% but not low ferritin levels were predictive for an adverse outcome. Anaemic patients with high ferritin levels, advanced inflammation, older age, low BMI, male gender, and reduced glomerular filtration rate had the worst prognosis. Conclusions: Anaemia and low tissue iron availability as reflected by TSAT <20% are negative predictors of outcome in patients with CHF. Systemic inflammation, renal function, BMI, age, and gender are important contributors for the clinical course. [ABSTRACT FROM AUTHOR]

Heart Failure is a severe chronic disease of the heart. Telehealth networks implement closed-loop healthcare paradigms for optimal treatment of the patients. For comprehensive documentation of medication treatment, health professionals create free text collaboration notes in addition to structured information. To make this valuable source of information available for adherence analyses, we developed classifiers for automated categorization of notes based on natural language processing, which allows filtering of relevant entries to spare data analysts from tedious manual screening. Furthermore, we identified potential improvements of the queries for structured treatment documentation. For 3,952 notes, the majority of the manually annotated category tags was medication-related. The highest F1-measure of our developed classifiers was 0.90. We conclude that our approach is a valuable tool to support adherence research based on datasets containing free-text entries. [ABSTRACT FROM AUTHOR]

Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first‐in‐class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double‐blind, placebo‐controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time‐averaged proportional change in N‐terminal pro‐brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks. [ABSTRACT FROM AUTHOR]

Background: Mutations in the LMNA gene are a common cause (6–8%) of dilated cardiomyopathy (DCM) leading to heart failure, a growing health care problem worldwide. The premature aging disease Hutchinson-Gilford syndrome (HGPS) is also caused by defined mutations in the LMNA gene resulting in activation of a cryptic splice donor site leading to a defective truncated prelamin A protein called progerin. Low levels of progerin are expressed in healthy individuals associated with ageing. Here, we aimed to address the role of progerin in dilated cardiomyopathy. Methods and results: mRNA expression of progerin was analyzed in heart tissue of DCM (n = 15) and non-failing hearts (n = 10) as control and in blood samples from patients with DCM (n = 56) and healthy controls (n = 10). Sequencing confirmed the expression of progerin mRNA in the human heart. Progerin mRNA levels derived from DCM hearts were significantly upregulated compared to controls (1.27 ± 0.42 vs. 0.81 ± 0.24; p = 0.005). In contrast, progerin mRNA levels in whole blood cells were not significantly different in DCM patients compared to controls. Linear regression analyses revealed that progerin mRNA in the heart is significantly negatively correlated to ejection fraction (r = -0.567, p = 0.003) and positively correlated to left ventricular enddiastolic diameter (r = 0.551, p = 0.004) but not with age of the heart per se. Progerin mRNA levels were not influenced by inflammation in DCM hearts. Immunohistochemistry and Immunofluorescence analysis confirmed increased expression of progerin protein in cell nuclei of DCM hearts associated with increased TUNEL+ apoptotic cells. Conclusion: Our data suggest that progerin is upregulated in human DCM hearts and strongly correlates with left ventricular remodeling. Progerin might be involved in progression of heart failure and myocardial aging. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases belong to the most common causes of death. Telehealth applications can help to improve therapy and support behavior change. It was the objective of the present work to construct and evaluate within a trial (25 patients) an automated feedback system for a telehealth application to support behavior change. We used a rule-based approach and constructed 26 rules in 9 categories. Rule design and implementation followed the principles of the Austrian Medical Product Law, resulting in an automated rule-based feedback system. Evaluations show high user satisfaction with 80% of all users perceiving the system as useful. [ABSTRACT FROM AUTHOR]