Artificial intelligence-based identification of left ventricular systolic dysfunction from 12-lead electrocardiograms: external validation and advanced application of an existing model.

Aims: The diagnostic application of artificial intelligence (AI)-based models to detect cardiovascular diseases from electrocardiograms (ECGs) evolves, and promising results were reported. However, external validation is not available for all published algorithms. The aim of this study was to validate an existing algorithm for the detection of left ventricular systolic dysfunction (LVSD) from 12-lead ECGs. Methods and results: Patients with digitalized data pairs of 12-lead ECGs and echocardiography (at intervals of ≤7 days) were retrospectively selected from the Heart Center Leipzig ECG and electronic medical records databases. A previously developed AI-based model was applied to ECGs and calculated probabilities for LVSD. The area under the receiver operating characteristic curve (AUROC) was computed overall and in cohorts stratified for baseline and ECG characteristics. Repeated echocardiography studies recorded ≥3 months after index diagnostics were used for follow-up (FU) analysis. At baseline, 42 291 ECG-echocardiography pairs were analysed, and AUROC for LVSD detection was 0.88. Sensitivity and specificity were 82% and 77% for the optimal LVSD probability cut-off based on Youden's J. AUROCs were lower in ECG subgroups with tachycardia, atrial fibrillation, and wide QRS complexes. In patients without LVSD at baseline and available FU, model-generated high probability for LVSD was associated with a four-fold increased risk of developing LVSD during FU. Conclusion: We provide the external validation of an existing AI-based ECG-analysing model for the detection of LVSD with robust performance metrics. The association of false positive LVSD screenings at baseline with a deterioration of ventricular function during FU deserves a further evaluation in prospective trials.

Patient perspectives on same-day discharge following catheter ablation for atrial fibrillation: results from a patient survey as part of the monocentric FAST AFA trial.

AIMS: Same-day discharge (SDD) following catheter ablation (CA) of atrial fibrillation (AF) was already introduced in selected facilities in Europe, but a widespread implementation has not yet succeeded. Data on patients' perspectives are lacking. Therefore, we conducted a survey to address patients' beliefs towards SDD and identify variables that are associated with their evaluation. METHODS AND RESULTS: As part of the prospective, monocentric FAST AFA trial, patients aged ≥20 years undergoing left atrial CA for AF were asked to participate in the survey consisting of a study-specific questionnaire, the AF knowledge scale, and pre-defined patient-reported outcome measures. The study cohort was stratified based on SDD willingness, and a logistic regression analysis was used to identify predictors for patients' valuation. Between 26 July 2021 and 01 July 2022, 256 of 376 screened patients consented to study participation of whom 248 (mean age 61.8 years, 33.9% female) completed the SDD survey. Of them, 50.0% were willing to have SDD concepts integrated into their clinical course with increased patient comfort (27.5%), shorter waiting times (14.6%), and a cost-efficient treatment (14.0%) being imaginable benefits. In contrast, expressed concerns included uncertainties with occurring complaints (50.6%), the insufficient recognition (47.8%), and treatment (48.9%) of complications. European Heart Rhythm Association class at baseline and inpatient treatments within the preceding year were predictors for SDD willingness whereas comorbidity burden or AF knowledge were not. CONCLUSION: We provide a detailed survey expressing patients' beliefs towards SDD following left atrial CA. Our findings may facilitate adequate patient selection to improve the future implementation of SDD programs in suitable cohorts.

A Digital Infrastructure for Cardiovascular Patient Care Based on Mobile Health Data and Patient-Reported Outcomes: Concept Details of the Helios TeleWear Project Including Preliminary Experiences.

BACKGROUND: Mobile health (mHealth) approaches are already having a fundamental impact on clinical practice in cardiovascular medicine. A variety of different health apps and wearable devices for capturing health data such as electrocardiograms (ECGs) exist. However, most mHealth technologies focus on distinct variables without integrating patients' quality of life, and the impact on clinical outcome measures of implementing those digital solutions into cardiovascular health care is still to be determined. OBJECTIVE: Within this document, we describe the TeleWear project, which was recently initiated as an approach for contemporary patient management integrating mobile-collected health data and the standardized mHealth-guided measurement of patient-reported outcomes (PROs) in patients with cardiovascular disease. METHODS: The specifically designed mobile app and clinical frontend form the central elements of our TeleWear infrastructure. Because of its flexible framework, the platform allows far-reaching customization with the possibility to add different mHealth data sources and respective questionnaires (patient-reported outcome measures). RESULTS: With initial focus on patients with cardiac arrhythmias, a feasibility study is currently carried out to assess wearable-recorded ECG and PRO transmission and its evaluation by physicians using the TeleWear app and clinical frontend. First experiences made during the feasibility study yielded positive results and confirmed the platform's functionality and usability. CONCLUSIONS: TeleWear represents a unique mHealth approach comprising PRO and mHealth data capturing. With the currently running TeleWear feasibility study, we aim to test and further develop the platform in a real-world setting. A randomized controlled trial including patients with atrial fibrillation that investigates PRO- and ECG-based clinical management based on the established TeleWear infrastructure will evaluate its clinical benefits. Widening the spectrum of health data collection and interpretation beyond the ECG and use of the TeleWear infrastructure in different patient subcohorts with focus on cardiovascular diseases are further milestones of the project with the ultimate goal to establish a comprehensive telemedical center entrenched by mHealth.

SARS-CoV-2 rapid antigen testing in the healthcare sector: A clinical prediction model for identifying false negative results.

OBJECTIVES: SARS-CoV-2 rapid antigen tests (RAT) provide fast identification of infectious patients when RT-PCR results are not immediately available. We aimed to develop a prediction model for identification of false negative (FN) RAT results. METHODS: In this multicenter trial, patients with documented paired results of RAT and RT-PCR between October 1st 2020 and January 31st 2021 were retrospectively analyzed regarding clinical findings. Variables included demographics, laboratory values and specific symptoms. Three different models were evaluated using Bayesian logistic regression. RESULTS: The initial dataset contained 4,076 patients. Overall sensitivity and specificity of RAT was 62.3% and 97.6%. 2,997 cases with negative RAT results (FN: 120; true negative: 2,877; reference: RT-PCR) underwent further evaluation after removal of cases with missing data. The best-performing model for predicting FN RAT results containing 10 variables yielded an area under the curve of 0.971. Sensitivity, specificity, PPV and NPV for 0.09 as cut-off value (probability for FN RAT) were 0.85, 0.99, 0.7 and 0.99. CONCLUSION: FN RAT results can be accurately identified through ten routinely available variables. Implementation of a prediction model in addition to RAT testing in clinical care can provide decision guidance for initiating appropriate hygiene measures and therefore helps avoiding nosocomial infections.

Patients' preferences regarding the digital capturing of patient-reported outcomes: planning the future follow-up in a prospective heart failure registry.

Aims: Digital health technologies have the potential to improve patient care sustainably. A digital capturing of patient-reported outcome measures (PROMs) could facilitate patients' surveillance and endpoint assessment within clinical trials especially in heart failure (HF) patients. However, data regarding the availability of digital infrastructure and patients' willingness to use digital health solutions are scarce. Therefore, we conducted a survey as part of a digital-based HF registry. Methods and results: The Helios Heart registry (H2-registry) has been introduced as a prospective registry being based on digitally augmented processes throughout the whole trial conduction from patients' selection to data collection and follow-up (FU). Patient-reported outcome measures are captured paper-based at recruitment, but patients are offered two digital solutions for FU. Overall, 125 patients (mean age 67.8 years, 34.4% female) were included in the single-centre run-in phase of 16 weeks. Of them, 52.0% were not interested in any digital contact as part of the FU. If digital PROM capturing was conceivable, a web-based solution (70.0%) was preferred to an application-based approach (30.0%). Discrepancies occurred regarding the availability of email accounts and smartphones. Patients in the non-digital group were older (72.0 years vs. 63.2 years, P < 0.01) and more frequently female (female sex, non-digital vs. digital group: 47.7% vs. 20.0%, P < 0.01). Conclusions: Our survey illustrated difficulties of implementing a digital FU to record PROMs in a contemporary HF cohort in particular among older patients. Further research is required to specify reasons in case of patients' unwillingness and to better tailor digital health solutions to patients' specific needs.

Alzheimer-related genes show accelerated evolution.

Alzheimer's disease (AD) is a neurodegenerative disorder of unknown cause with complex genetic and environmental traits. While AD is extremely prevalent in human elderly, it hardly occurs in non-primate mammals and even non-human-primates develop only an incomplete form of the disease. This specificity of AD to human clearly implies a phylogenetic aspect. Still, the evolutionary dimension of AD pathomechanism remains difficult to prove and has not been established so far. To analyze the evolutionary age and dynamics of AD-associated-genes, we established the AD-associated genome-wide RNA-profile comprising both protein-coding and non-protein-coding transcripts. We than applied a systematic analysis on the conservation of splice-sites as a measure of gene-structure based on multiple alignments across vertebrates of homologs of AD-associated-genes. Here, we show that nearly all AD-associated-genes are evolutionarily old and did not originate later in evolution than not-AD-associated-genes. However, the gene-structures of loci, that exhibit AD-associated changes in their expression, evolve faster than the genome at large. While protein-coding-loci exhibit an enhanced rate of small changes in gene structure, non-coding loci show even much larger changes. The accelerated evolution of AD-associated-genes indicates a more rapid functional adaptation of these genes. In particular AD-associated non-coding-genes play an important, as yet largely unexplored, role in AD. This phylogenetic trait indicates that recent adaptive evolution of human brain is causally involved in basic principles of neurodegeneration. It highlights the necessity for a paradigmatic change of our disease-concepts and to reconsider the appropriateness of current animal-models to develop disease-modifying strategies that can be translated to human.

Evolutionary clues in lncRNAs.

The diversity of long non-coding RNAs (lncRNAs) in the human transcriptome is in stark contrast to the sparse exploration of their functions concomitant with their conservation and evolution. The pervasive transcription of the largely non-coding human genome makes the evolutionary age and conservation patterns of lncRNAs to a topic of interest. Yet it is a fairly unexplored field and not that easy to determine as for protein-coding genes. Although there are a few experimentally studied cases, which are conserved at the sequence level, most lncRNAs exhibit weak or untraceable primary sequence conservation. Recent studies shed light on the interspecies conservation of secondary structures among lncRNA homologs by using diverse computational methods. This highlights the importance of structure on functionality of lncRNAs as opposed to the poor impact of primary sequence changes. Further clues in the evolution of lncRNAs are given by selective constraints on non-coding gene structures (e.g., promoters or splice sites) as well as the conservation of prevalent spatio-temporal expression patterns. However, a rapid evolutionary turnover is observable throughout the heterogeneous group of lncRNAs. This still gives rise to questions about its functional meaning. WIREs RNA 2017, 8:e1376. doi: 10.1002/wrna.1376 For further resources related to this article, please visit the WIREs website.

Comparison of splice sites reveals that long noncoding RNAs are evolutionarily well conserved.

Large-scale RNA sequencing has revealed a large number of long mRNA-like transcripts (lncRNAs) that do not code for proteins. The evolutionary history of these lncRNAs has been notoriously hard to study systematically due to their low level of sequence conservation that precludes comprehensive homology-based surveys and makes them nearly impossible to align. An increasing number of special cases, however, has been shown to be at least as old as the vertebrate lineage. Here we use the conservation of splice sites to trace the evolution of lncRNAs. We show that >85% of the human GENCODE lncRNAs were already present at the divergence of placental mammals and many hundreds of these RNAs date back even further. Nevertheless, we observe a fast turnover of intron/exon structures. We conclude that lncRNA genes are evolutionary ancient components of vertebrate genomes that show an unexpected and unprecedented evolutionary plasticity. We offer a public web service (http://splicemap.bioinf.uni-leipzig.de) that allows to retrieve sets of orthologous splice sites and to produce overview maps of evolutionarily conserved splice sites for visualization and further analysis. An electronic supplement containing the ncRNA data sets used in this study is available at http://www.bioinf.uni-leipzig.de/publications/supplements/12-001.

Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein-coding RNAs.

BACKGROUND: The genome is pervasively transcribed but most transcripts do not code for proteins, constituting non-protein-coding RNAs. Despite increasing numbers of functional reports of individual long non-coding RNAs (lncRNAs), assessing the extent of functionality among the non-coding transcriptional output of mammalian cells remains intricate. In the protein-coding world, transcripts differentially expressed in the context of processes essential for the survival of multicellular organisms have been instrumental in the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identified lncRNAs expressed differentially in response to oncologically relevant processes and cell-cycle, p53 and STAT3 pathways, using tiling arrays. RESULTS: We found that up to 80% of the pathway-triggered transcriptional responses are non-coding. Among these we identified very large macroRNAs with pathway-specific expression patterns and demonstrated that these are likely continuous transcripts. MacroRNAs contain elements conserved in mammals and sauropsids, which in part exhibit conserved RNA secondary structure. Comparing evolutionary rates of a macroRNA to adjacent protein-coding genes suggests a local action of the transcript. Finally, in different grades of astrocytoma, a tumor disease unrelated to the initially used cell lines, macroRNAs are differentially expressed. CONCLUSIONS: It has been shown previously that the majority of expressed non-ribosomal transcripts are non-coding. We now conclude that differential expression triggered by signaling pathways gives rise to a similar abundance of non-coding content. It is thus unlikely that the prevalence of non-coding transcripts in the cell is a trivial consequence of leaky or random transcription events.

Atypical RNAs in the coelacanth transcriptome.

Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome. Surprisingly, the majority of the circularizing and trans-connecting splice junctions are unique to atypical forms, that is, are not used in normal isoforms.