Consumer wearable devices for evaluation of heart rate control using digoxin versus beta-blockers: the RATE-AF randomized trial.

Consumer-grade wearable technology has the potential to support clinical research and patient management. Here, we report results from the RATE-AF trial wearables study, which was designed to compare heart rate in older, multimorbid patients with permanent atrial fibrillation and heart failure who were randomized to treatment with either digoxin or beta-blockers. Heart rate (n = 143,379,796) and physical activity (n = 23,704,307) intervals were obtained from 53 participants (mean age 75.6 years (s.d. 8.4), 40% women) using a wrist-worn wearable linked to a smartphone for 20 weeks. Heart rates in participants treated with digoxin versus beta-blockers were not significantly different (regression coefficient 1.22 (95% confidence interval (CI) -2.82 to 5.27; P = 0.55); adjusted 0.66 (95% CI -3.45 to 4.77; P = 0.75)). No difference in heart rate was observed between the two groups of patients after accounting for physical activity (P = 0.74) or patients with high activity levels (≥30,000 steps per week; P = 0.97). Using a convolutional neural network designed to account for missing data, we found that wearable device data could predict New York Heart Association functional class 5 months after baseline assessment similarly to standard clinical measures of electrocardiographic heart rate and 6-minute walk test (F1 score 0.56 (95% CI 0.41 to 0.70) versus 0.55 (95% CI 0.41 to 0.68); P = 0.88 for comparison). The results of this study indicate that digoxin and beta-blockers have equivalent effects on heart rate in atrial fibrillation at rest and on exertion, and suggest that dynamic monitoring of individuals with arrhythmia using wearable technology could be an alternative to in-person assessment. ClinicalTrials.gov identifier: NCT02391337 .

Remote monitoring of atrial fibrillation recurrence using mHealth technology (REMOTE-AF).

Aims: This proof-of-concept study sought to evaluate changes in heart rate (HR) obtained from a consumer wearable device and compare against implantable loop recorder (ILR)-detected recurrence of atrial fibrillation (AF) and atrial tachycardia (AT) after AF ablation. Methods and results: REMOTE-AF (NCT05037136) was a prospectively designed sub-study of the CASA-AF randomized controlled trial (NCT04280042). Participants without a permanent pacemaker had an ILR implanted at their index ablation procedure for longstanding persistent AF. Heart rate and step count were continuously monitored using photoplethysmography (PPG) from a commercially available wrist-worn wearable. Photoplethysmography-recorded HR data were pre-processed with noise filtration and episodes at 1-min interval over 30 min of HR elevations (Z-score = 2) were compared with corresponding ILR data. Thirty-five patients were enrolled, with mean age 70.3 ± 6.8 years and median follow-up 10 months (interquartile range 8-12 months). Implantable loop recorder analysis revealed 17 out of 35 patients (49%) had recurrence of AF/AT. Compared with ILR recurrence, wearable-derived elevations in HR ≥ 110 beats per minute had a sensitivity of 95.3%, specificity 54.1%, positive predictive value (PPV) 15.8%, negative predictive value (NPV) 99.2%, and overall accuracy 57.4%. With PPG-recorded HR elevation spikes (non-exercise related), the sensitivity was 87.5%, specificity 62.2%, PPV 39.2%, NPV 92.3%, and overall accuracy 64.0% in the entire patient cohort. In the AF/AT recurrence only group, sensitivity was 87.6%, specificity 68.3%, PPV 53.6%, NPV 93.0%, and overall accuracy 75.0%. Conclusion: Consumer wearable devices have the potential to contribute to arrhythmia detection after AF ablation. Study Registration: ClinicalTrials.gov Identifier: NCT05037136 https://clinicaltrials.gov/ct2/show/NCT05037136.

Artificial intelligence to enhance clinical value across the spectrum of cardiovascular healthcare.

Artificial intelligence (AI) is increasingly being utilized in healthcare. This article provides clinicians and researchers with a step-wise foundation for high-value AI that can be applied to a variety of different data modalities. The aim is to improve the transparency and application of AI methods, with the potential to benefit patients in routine cardiovascular care. Following a clear research hypothesis, an AI-based workflow begins with data selection and pre-processing prior to analysis, with the type of data (structured, semi-structured, or unstructured) determining what type of pre-processing steps and machine-learning algorithms are required. Algorithmic and data validation should be performed to ensure the robustness of the chosen methodology, followed by an objective evaluation of performance. Seven case studies are provided to highlight the wide variety of data modalities and clinical questions that can benefit from modern AI techniques, with a focus on applying them to cardiovascular disease management. Despite the growing use of AI, further education for healthcare workers, researchers, and the public are needed to aid understanding of how AI works and to close the existing gap in knowledge. In addition, issues regarding data access, sharing, and security must be addressed to ensure full engagement by patients and the public. The application of AI within healthcare provides an opportunity for clinicians to deliver a more personalized approach to medical care by accounting for confounders, interactions, and the rising prevalence of multi-morbidity.

Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study.

Importance: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. Objective: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness. Design, Setting, and Participants: This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021. Exposures: Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses. Main Outcomes and Measures: Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P < 1.1 × 10-4. Differential gene expression in AHBA data was modeled in brain regions mapped to areas significant in MR analyses; genes were tested for biological and disease overrepresentation in annotation databases and for connectivity in protein-protein interaction networks. Results: Of 20 688 participants in the UK Biobank sample, 10 828 (52.3%) were female, and the mean (SD) age was 55.5 (7.5) years. In the UK Biobank sample, genetically predicted levels of IL-6 were associated with GMV in the middle temporal cortex (z score, 5.76; P = 8.39 × 10-9), inferior temporal (z score, 3.38; P = 7.20 × 10-5), fusiform (z score, 4.70; P = 2.60 × 10-7), and frontal (z score, -3.59; P = 3.30 × 10-5) cortex together with CT in the superior frontal region (z score, -5.11; P = 3.22 × 10-7). No significant associations were found for IL-1, IL-2, CRP, or BDNF after correction for multiple comparison. In the AHBA sample, 5 of 6 participants (83%) were male, and the mean (SD) age was 42.5 (13.4) years. Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus (MTG), which further formed a highly connected protein-protein interaction network with IL-6 (enrichment test of expected vs observed network given the prevalence and degree of interactions in the STRING database: 43 nodes/30 edges observed vs 8 edges expected; mean node degree, 1.4; genome-wide significance, P = 4.54 × 10-9). MTG differentially expressed genes that were functionally enriched for biological processes in schizophrenia, autism spectrum disorder, and epilepsy. Conclusions and Relevance: In this study, genetically determined IL-6 was associated with brain structure and potentially affects areas implicated in developmental neuropsychiatric disorders, including schizophrenia and autism.

A comparison of temporal pathways to self-harm in young people compared to adults: A pilot test of the Card Sort Task for Self-harm online using Indicator Wave Analysis.

Background: Self-harm is complex, multifaceted, and dynamic, typically starts in adolescence, and is prevalent in young people. A novel research tool (the Card Sort Task for Self-harm; CaTS) offers a systematic approach to understanding this complexity by charting the dynamic interplay between multidimensional factors in the build-up to self-harm. Sequential analysis of CaTS has revealed differences in key factors between the first and the most recent episode of self-harm in adolescence. Rates of self-harm typically decline post-adolescence, but self-harm can continue into adulthood. A comparison between factors linked to self-harm in young people vs. adults will inform an understanding of how risk unfolds over time and clarify age-specific points for intervention. A pilot online adaptation (CaTS-online) and a new method (Indicator Wave Analysis; IWA) were used to assess key factors in the build-up to self-harm. Methods: Community-based young people (n = 66; 18-25 years, M = 21.4; SD = 1.8) and adults (n = 43; 26-57 years, M = 35; SD = 8.8) completed CaTS-online, documenting thoughts, feelings, events, and behaviours over a 6-month timeline for the first ever and most recent self-harm. A notable interdependence between factors and time points was identified using IWA. Results: Positive emotion at and immediately after self-harm exceeded the threshold for both groups for both episodes. Feeling better following self-harm was more pronounced for the first-ever episodes. Impulsivity was an important immediate antecedent to self-harm for both groups at both episodes but most markedly for young people. Acquired capability was notable for adults' most recent episodes, suggesting this develops over time. Burdensomeness was only more notable for adults and occurred 1 week prior to a recent episode. Both groups revealed patterns of accessing support that were helpful and unhelpful. Conclusion: Commonalities and differences in the temporal organisation of factors leading to and following self-harm were identified in young people and adult pathways which shed light on age-specific factors and possible points of intervention. This has implications for clinical support and services around approaches to positive feelings after self-harm (especially for first-ever self-harm), feeling of burdensomeness, impulsivity, and acquired capability leading up to self-harm. Support is provided for card-sort approaches that enable the investigation of the complex and dynamic nature of pathways to self-harm.

Redefining ß-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis.

BACKGROUND: Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of ß-blocker efficacy in patients with sinus rhythm and atrial fibrillation. METHODS: Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of ß blockers. All-cause mortality during median 1·3 years of follow-up was assessed by intention to treat, stratified by electrocardiographic heart rhythm. The number of clusters and dimensions was determined objectively, with results validated using a leave-one-trial-out approach. This study was prospectively registered with ClinicalTrials.gov (NCT00832442) and the PROSPERO database of systematic reviews (CRD42014010012). FINDINGS: 15 659 patients with heart failure and LVEF of less than 50% were included, with median age 65 years (IQR 56-72) and LVEF 27% (IQR 21-33). 3708 (24%) patients were women. In sinus rhythm (n=12 822), most clusters demonstrated a consistent overall mortality benefit from ß blockers, with odds ratios (ORs) ranging from 0·54 to 0·74. One cluster in sinus rhythm of older patients with less severe symptoms showed no significant efficacy (OR 0·86, 95% CI 0·67-1·10; p=0·22). In atrial fibrillation (n=2837), four of five clusters were consistent with the overall neutral effect of ß blockers versus placebo (OR 0·92, 0·77-1·10; p=0·37). One cluster of younger atrial fibrillation patients at lower mortality risk but similar LVEF to average had a statistically significant reduction in mortality with ß blockers (OR 0·57, 0·35-0·93; p=0·023). The robustness and consistency of clustering was confirmed for all models (p<0·0001 vs random), and cluster membership was externally validated across the nine independent trials. INTERPRETATION: An artificial intelligence-based clustering approach was able to distinguish prognostic response from ß blockers in patients with heart failure and reduced LVEF. This included patients in sinus rhythm with suboptimal efficacy, as well as a cluster of patients with atrial fibrillation where ß blockers did reduce mortality. FUNDING: Medical Research Council, UK, and EU/EFPIA Innovative Medicines Initiative BigData@Heart.