AI-enhanced reconstruction of the 12-lead electrocardiogram via 3-leads with accurate clinical assessment.

The 12-lead electrocardiogram (ECG) is an integral component to the diagnosis of a multitude of cardiovascular conditions. It is performed using a complex set of skin surface electrodes, limiting its use outside traditional clinical settings. We developed an artificial intelligence algorithm, trained over 600,000 clinically acquired ECGs, to explore whether fewer leads as input are sufficient to reconstruct a 12-lead ECG. Two limb leads (I and II) and one precordial lead (V3) were required to generate a reconstructed 12-lead ECG highly correlated with the original ECG. An automatic algorithm for detection of ECG features consistent with acute myocardial infarction (MI) performed similarly for original and reconstructed ECGs (AUC = 0.95). When interpreted by cardiologists, reconstructed ECGs achieved an accuracy of 81.4 ± 5.0% in identifying ECG features of ST-segment elevation MI, comparable with the original 12-lead ECGs (accuracy 84.6 ± 4.6%). These results will impact development efforts to innovate ECG acquisition methods with simplified tools in non-specialized settings.

Engagement with health research summaries via digital communication to All of Us participants.

OBJECTIVE: Summaries of health research can be a complementary way to return value to participants. We assess how research participants engage with summaries via email communication and how this can be improved. MATERIALS AND METHODS: We look at correlations between demographic subgroups and engagement in a longitudinal dataset of 305 626 participants (77% are classified as underrepresented in biomedical research) from the All of Us Research Program. We compare this against engagement with other program communications and use impact evaluations (N = 421 510) to measure the effect of tailoring communication by (1) eliciting content preferences, (2) Spanish focused content, (3) informational videos, and (4) article content in the email subject line. RESULTS: Between March 2020 and October 2021, research summaries reached 67% of enrolled participants, outperforming other program communication (60%) and return of results (31%), which have a high uptake rate but have been extended to a subset of eligible participants. While all demographic subgroups engage with research summaries, participants with higher income, educational attainment, White, and older than 45 years open and click content most often. Surfacing article content in the email subject line and Spanish focused content had negative effects on engagement. Video and social media content and eliciting preferences led to a small directional increase in clicks. DISCUSSION: Further individualization of tailoring efforts may be needed to drive larger engagement effects (eg, delivering multiple articles in line with stated preferences, expanding preference options). Our findings are likely a conservative representation of engagement effects, given the coarseness of our click rate measure. CONCLUSIONS: Health research summaries show promise as a way to return value to research participants, especially if individual-level results cannot be returned. Personalization of communication requires testing to determine whether efforts are having the expected effect.

Feasibility of wearable sensor signals and self-reported symptoms to prompt at-home testing for acute respiratory viruses in the USA (DETECT-AHEAD): a decentralised, randomised controlled trial.

BACKGROUND: Early identification of an acute respiratory infection is important for reducing transmission and enabling earlier therapeutic intervention. We aimed to prospectively evaluate the feasibility of home-based diagnostic self-testing of viral pathogens in individuals prompted to do so on the basis of self-reported symptoms or individual changes in physiological parameters detected via a wearable sensor. METHODS: DETECT-AHEAD was a prospective, decentralised, randomised controlled trial carried out in a subpopulation of an existing cohort (DETECT) of individuals enrolled in a digital-only observational study in the USA. Participants aged 18 years or older were randomly assigned (1:1:1) with a block randomisation scheme stratified by under-represented in biomedical research status. All participants were offered a wearable sensor (Fitbit Sense smartwatch). Participants in groups 1 and 2 received an at-home self-test kit (Alveo be.well) for two acute respiratory viral pathogens: SARS-CoV-2 and respiratory syncytial virus. Participants in group 1 could be alerted through the DETECT study app to take the at-home test on the basis of changes in their physiological data (as detected by our algorithm) or due to self-reported symptoms; those in group 2 were prompted via the app to self-test only due to symptoms. Group 3 served as the control group, without alerts or home testing capability. The primary endpoints, assessed on an intention-to-treat basis, were the number of acute respiratory infections presented (self-reported) and diagnosed (electronic health record), and the number of participants using at-home testing in groups 1 and 2. This trial is registered with ClinicalTrials.gov, NCT04336020. FINDINGS: Between Sept 28 and Dec 30, 2021, 450 participants were recruited and randomly assigned to group 1 (n=149), group 2 (n=151), or group 3 (n=150). 179 (40%) participants were male, 264 (59%) were female, and seven (2%) identified as other. 232 (52%) were from populations historically under-represented in biomedical research. 118 (39%) of the 300 participants in groups 1 and 2 were prompted to self-test, with 61 (52%) successfully completing self-testing. Participants were prompted to home-test more frequently due to symptoms (41 [28%] in group 1 and 51 [34%] in group 2) than due to detected physiological changes (26 [17%] in group 1). Significantly more participants in group 1 received alerts to test than did those in group 2 (67 [45%] vs 51 [34%]; p=0·047). Of the 61 individuals who were prompted to test and successfully did so, 19 (31%) tested positive for a viral pathogen-all for SARS-CoV-2. The individuals diagnosed as positive for SARS-CoV-2 in the electronic health record were eight (5%) in group 1, four (3%) in group 2, and two (1%) in group 3, but it was difficult to confirm if they were tied to symptomatic episodes documented in the trial. There were no adverse events. INTERPRETATION: In this direct-to-participant trial, we showed early feasibility of a decentralised programme to prompt individuals to use a viral pathogen diagnostic test based on symptoms tracked in the study app or physiological changes detected using a wearable sensor. Barriers to adequate participation and performance were also identified, which would need to be addressed before large-scale implementation. FUNDING: Janssen Pharmaceuticals.

A pilot study exploring novel contexts for out-of-office blood pressure measurement.

Introduction: Out-of-office blood pressure (BP) monitoring is increasingly valuable in the diagnosis and management of hypertension. With advances in wearable BP technologies, the ability to gain insight into BP outside of traditional centers of care has expanded greatly. Methods: Here we explore the usability of a novel, wrist-worn BP cuff monitor for out-of-office data collection with participants following digital cues rather than in-person instruction. Transmitted measurements were used to evaluate BP variation with the time of day and day of week, BP variation with mood, and orthostatic measurements. Results: Fifty participants, with a mean age of 44.5 years, were enrolled and received the BP monitor. 82% of the participants transmitted data via the smartphone application, and the median wear time of the device during the 4-week study was 11 days (IQR 8-17). Discussion: This prospective digital pilot study illustrates the usability of wearable oscillometric BP technology combined with digital cues via a smartphone application to obtain complex out-of-office BP measurements, including orthostatic vital signs and BP associated with emotion. 25 out of 32 participants who attempted orthostatic vital signs based on in-app instruction were able to do so correctly, while 24 participants transmitted BP readings associated with emotion, with a significant difference in BP noted between calm and stressed emotional states.

AI-Enhanced Reconstruction of the 12-Lead Electrocardiogram via 3-Leads with Accurate Clinical Assessment.

The 12-lead electrocardiogram (ECG) is an integral component to the diagnosis of a multitude of cardiovascular conditions. It is performed using a complex set of skin surface electrodes, limiting its use outside traditional clinical settings. We developed an artificial intelligence algorithm, trained over 600,000 clinically acquired ECGs, to explore whether fewer leads as input are sufficient to reconstruct a full 12-lead ECG. Two limb leads (I and II) and one precordial lead (V3) were required to generate a reconstructed synthetic 12-lead ECG highly correlated with the original ECG. An automatic algorithm for detection of acute myocardial infarction (MI) performed similarly for original and reconstructed ECGs (AUC=0.94). When interpreted by cardiologists, reconstructed ECGs achieved an accuracy of 81.4±5.0% in identifying ST elevation MI, comparable with the original 12-lead ECGs (accuracy 84.6±4.6%). These results will impact development efforts to innovate ECG acquisition methods with simplified tools in non-specialized settings.

Objectively measured peri-vaccination sleep does not predict COVID-19 breakthrough infection.

Prior studies have shown that sleep duration peri-vaccination influences an individual's antibody response. However, whether peri-vaccination sleep affects real-world vaccine effectiveness is unknown. Here, we tested whether objectively measured sleep around COVID-19 vaccination affected breakthrough infection rates. DETECT is a study of digitally recruited participants who report COVID-19-related information, including vaccination and illness data. Objective sleep data are also recorded through activity trackers. We compared the impact of sleep duration, sleep efficiency, and frequency of awakenings on reported breakthrough infection after the 2nd vaccination and 1st COVID-19 booster. Logistic regression models were created to examine if sleep metrics predicted COVID-19 breakthrough infection independent of age and gender. Self-reported breakthrough COVID-19 infection following 2nd COVID-19 vaccination and 1st booster. 256 out of 5265 individuals reported a breakthrough infection after the 2nd vaccine, and 581 out of 2583 individuals reported a breakthrough after the 1st booster. There was no difference in sleep duration between those with and without breakthrough infection. Increased awakening frequency was associated with breakthrough infection after the 1st booster with 3.01 ± 0.65 awakenings/hour in the breakthrough group compared to 2.82 ± 0.65 awakenings/hour in those without breakthrough (P < 0.001). Cox proportional hazards modeling showed that age < 60 years (hazard ratio 2.15, P < 0.001) and frequency of awakenings (hazard ratio 1.17, P = 0.019) were associated with breakthrough infection after the 1st booster. Sleep duration was not associated with breakthrough infection after COVID vaccination. While increased awakening frequency during sleep was associated with breakthrough infection beyond traditional risk factors, the clinical implications of this finding are unclear.

Prediction of atrial fibrillation from at-home single-lead ECG signals without arrhythmias.

Early identification of atrial fibrillation (AF) can reduce the risk of stroke, heart failure, and other serious cardiovascular outcomes. However, paroxysmal AF may not be detected even after a two-week continuous monitoring period. We developed a model to quantify the risk of near-term AF in a two-week period, based on AF-free ECG intervals of up to 24 h from 459,889 patch-based ambulatory single-lead ECG (modified lead II) recordings of up to 14 days. A deep learning model was used to integrate ECG morphology data with demographic and heart rhythm features toward AF prediction. Observing a 1-day AF-free ECG recording, the model with deep learning features produced the most accurate prediction of near-term AF with an area under the curve AUC = 0.80 (95% confidence interval, CI = 0.79-0.81), significantly improving discrimination compared to demographic metrics alone (AUC 0.67; CI = 0.66-0.68). Our model was able to predict incident AF over a two-week time frame with high discrimination, based on AF-free single-lead ECG recordings of various lengths. Application of the model may enable a digital strategy for improving diagnostic capture of AF by risk stratifying individuals with AF-negative ambulatory monitoring for prolonged or recurrent monitoring, potentially leading to more rapid initiation of treatment.

Heart Rate Variability in Psychiatric Disorders: A Systematic Review.

Introduction: Heart rate variability (HRV) is a measure of the fluctuation in time interval between consecutive heart beats. Decreased heart rate variability has been shown to have associations with autonomic dysfunction in psychiatric conditions such as depression, substance abuse, anxiety, and schizophrenia, although its use as a prognostic tool remains highly debated. This study aims to review the current literature on heart rate variability as a diagnostic and prognostic tool in psychiatric populations. Methods: A literature search was conducted using the MEDLINE, EMBASE, Cochrane, and PsycINFO libraries to identify full-text studies involving adult psychiatric populations that reported HRV measurements. From 1647 originally identified, 31 studies were narrowed down through an abstract and full-text screen. Studies were excluded if they enrolled adolescents or children, used animal models, enrolled patients with another primary diagnosis other than psychiatric as outlined by the diagnostic and statistical manual of mental disorders (DSM) V, or if they assessed HRV in the context of treatment rather than diagnosis. Study quality assessment was conducted using a modified Downs and Blacks quality assessment tool for observational rather than interventional studies. Data were reported in four tables: 1) summarizing study characteristics, 2) methods of HRV detection, 3) key findings and statistics, and 4) quality assessment. Results: There is significant variability between studies in their methodology of recording as well as reporting HRV, which makes it difficult to meaningfully interpret data that is clinically applicable due to the presence of significant bias in existing studies. The presence of an association between HRV and the severity of various psychiatric disorders, however, remains promising. Conclusion: Future studies should be done to further explore how HRV parameters may be used to enhance the diagnosis and prognosis of several psychiatric disorders.

Prevalence of Positive COVID-19 Test Results Collected by Digital Self-report in the US and Germany.

This cohort study examines traditional surveillance and self-reported COVID-19 test result data collected from independent smartphone app­based studies in the US and Germany.

Sensor-based surveillance for digitising real-time COVID-19 tracking in the USA (DETECT): a multivariable, population-based, modelling study.

BACKGROUND: Traditional viral illness surveillance relies on in-person clinical or laboratory data, paper-based data collection, and outdated technology for data transfer and aggregation. We aimed to assess whether continuous sensor data can provide an early warning signal for COVID-19 activity as individual physiological and behavioural changes might precede symptom onset, care seeking, and diagnostic testing. METHODS: This multivariable, population-based, modelling study recruited adult (aged ≥18 years) participants living in the USA who had a smartwatch or fitness tracker on any device that connected to Apple HealthKit or Google Fit and had joined the DETECT study by downloading the MyDataHelps app. In the model development cohort, we included people who had participated in DETECT between April 1, 2020, and Jan 14, 2022. In the validation cohort, we included individuals who had participated between Jan 15 and Feb 15, 2022. When a participant joins DETECT, they fill out an intake survey of demographic information, including their ZIP code (postal code), and surveys on symptoms, symptom onset, and viral illness test dates and results, if they become unwell. When a participant connects their device, historical sensor data are collected, if available. Sensor data continue to be collected unless a participant withdraws from the study. Using sensor data, we collected each participant's daily resting heart rate and step count during the entire study period and identified anomalous sensor days, in which resting heart rate was higher than, and step count was lower than, a specified threshold calculated for each individual by use of their baseline data. The proportion of users with anomalous data each day was used to create a 7-day moving average. For the main cohort, a negative binomial model predicting 7-day moving averages for COVID-19 case counts, as reported by the Centers for Disease Control and Prevention (CDC), in real time, 6 days in the future, and 12 days in the future in the USA and California was fitted with CDC-reported data from 3 days before alone (H0) or in combination with anomalous sensor data (H1). We compared the predictions with Pearson correlation. We then validated the model in the validation cohort. FINDINGS: Between April 1, 2020, and Jan 14, 2022, 35 842 participants enrolled in DETECT, of whom 4006 in California and 28 527 in the USA were included in our main cohort. The H1 model significantly outperformed the H0 model in predicting the 7-day moving average COVID-19 case counts in California and the USA. For example, Pearson correlation coefficients for predictions 12 days in the future increased by 32·9% in California (from 0·70 [95% CI 0·65-0·73] to 0·93 [0·92-0·94]) and by 12·2% (from 0·82 [0·79-0·84] to 0·92 [0·91-0·93]) in the USA from the H0 model to the H1 model. Our validation model also showed significant correlations for predictions in real time, 6 days in the future, and 12 days in the future. INTERPRETATION: Our study showed that passively collected sensor data from consenting participants can provide real-time disease tracking and forecasting. With a growing population of wearable technology users, these sensor data could be integrated into viral surveillance programmes. FUNDING: The National Center for Advancing Translational Sciences of the US National Institutes of Health, The Rockefeller Foundation, and Amazon Web Services.

Smartphone apps in the COVID-19 pandemic.

At the beginning of the COVID-19 pandemic, analog tools such as nasopharyngeal swabs for PCR tests were center stage and the major prevention tactics of masking and physical distancing were a throwback to the 1918 influenza pandemic. Overall, there has been scant regard for digital tools, particularly those based on smartphone apps, which is surprising given the ubiquity of smartphones across the globe. Smartphone apps, given accessibility in the time of physical distancing, were widely used for tracking, tracing and educating the public about COVID-19. Despite limitations, such as concerns around data privacy, data security, digital health illiteracy and structural inequities, there is ample evidence that apps are beneficial for understanding outbreak epidemiology, individual screening and contact tracing. While there were successes and failures in each category, outbreak epidemiology and individual screening were substantially enhanced by the reach of smartphone apps and accessory wearables. Continued use of apps within the digital infrastructure promises to provide an important tool for rigorous investigation of outcomes both in the ongoing outbreak and in future epidemics.

Inter-individual variation in objective measure of reactogenicity following COVID-19 vaccination via smartwatches and fitness bands.

The ability to identify who does or does not experience the intended immune response following vaccination could be of great value in not only managing the global trajectory of COVID-19 but also helping guide future vaccine development. Vaccine reactogenicity can potentially lead to detectable physiologic changes, thus we postulated that we could detect an individual's initial physiologic response to a vaccine by tracking changes relative to their pre-vaccine baseline using consumer wearable devices. We explored this possibility using a smartphone app-based research platform that enabled volunteers (39,701 individuals) to share their smartwatch data, as well as self-report, when appropriate, any symptoms, COVID-19 test results, and vaccination information. Of 7728 individuals who reported at least one vaccination dose, 7298 received an mRNA vaccine, and 5674 provided adequate data from the peri-vaccine period for analysis. We found that in most individuals, resting heart rate (RHR) increased with respect to their individual baseline after vaccination, peaked on day 2, and returned to normal by day 6. This increase in RHR was greater than one standard deviation above individuals' normal daily pattern in 47% of participants after their second vaccine dose. Consistent with other reports of subjective reactogenicity following vaccination, we measured a significantly stronger effect after the second dose relative to the first, except those who previously tested positive to COVID-19, and a more pronounced increase for individuals who received the Moderna vaccine. Females, after the first dose only, and those aged <40 years, also experienced a greater objective response after adjusting for possible confounding factors. These early findings show that it is possible to detect subtle, but important changes from an individual's normal as objective evidence of reactogenicity, which, with further work, could prove useful as a surrogate for vaccine-induced immune response.

Passive detection of COVID-19 with wearable sensors and explainable machine learning algorithms.

Individual smartwatch or fitness band sensor data in the setting of COVID-19 has shown promise to identify symptomatic and pre-symptomatic infection or the need for hospitalization, correlations between peripheral temperature and self-reported fever, and an association between changes in heart-rate-variability and infection. In our study, a total of 38,911 individuals (61% female, 15% over 65) have been enrolled between March 25, 2020 and April 3, 2021, with 1118 reported testing positive and 7032 negative for COVID-19 by nasopharyngeal PCR swab test. We propose an explainable gradient boosting prediction model based on decision trees for the detection of COVID-19 infection that can adapt to the absence of self-reported symptoms and to the available sensor data, and that can explain the importance of each feature and the post-test-behavior for the individuals. We tested it in a cohort of symptomatic individuals who exhibited an AUC of 0.83 [0.81-0.85], or AUC = 0.78 [0.75-0.80] when considering only data before the test date, outperforming state-of-the-art algorithm in these conditions. The analysis of all individuals (including asymptomatic and pre-symptomatic) when self-reported symptoms were excluded provided an AUC of 0.78 [0.76-0.79], or AUC of 0.70 [0.69-0.72] when considering only data before the test date. Extending the use of predictive algorithms for detection of COVID-19 infection based only on passively monitored data from any device, we showed that it is possible to scale up this platform and apply the algorithm in other settings where self-reported symptoms can not be collected.

The Physiologic Response to COVID-19 Vaccination.

Two mRNA vaccines and one adenovirus-based vaccine against SARS CoV-2 are currently being distributed at scale in the United States. Objective evidence of a specific individual's physiologic response to that vaccine are not routinely tracked but may offer insights into the acute immune response and personal and/or vaccine characteristics associated with that. We explored this possibility using a smartphone app-based research platform developed early in the pandemic that enabled volunteers (38,911 individuals between 25 March 2020 and 4 April 2021) to share their smartwatch and activity tracker data, as well as self-report, when appropriate, any symptoms, COVID-19 test results and vaccination dates and type. Of 4,110 individuals who reported at least one mRNA vaccination dose, 3,312 provided adequate resting heart rate data from the peri-vaccine period for analysis. We found changes in resting heart rate with respect to an individual baseline increased the days after vaccination, peaked on day 2, and returned to normal on day 6, with a much stronger effect after second dose with respect to first dose (average changes 1.6 versus 0.5 beats per minute). The changes were more pronounced for individuals who received the Moderna vaccine (on both doses), those who previously tested positive to COVID-19 (on dose 1), and for individuals aged <40 years, after adjusting for possible confounding factors. Taking advantage of continuous passive data from personal sensors could potentially enable the identification of a digital fingerprint of inflammation, which might prove useful as a surrogate for vaccine-induced immune response.

A Comprehensive Explanation Framework for Biomedical Time Series Classification.

In this study, we propose a post-hoc explainability framework for deep learning models applied to quasi-periodic biomedical time-series classification. As a case study, we focus on the problem of atrial fibrillation (AF) detection from electrocardiography signals, which has strong clinical relevance. Starting from a state-of-the-art pretrained model, we tackle the problem from two different perspectives: global and local explanation. With global explanation, we analyze the model behavior by looking at entire classes of data, showing which regions of the input repetitive patterns have the most influence for a specific outcome of the model. Our explanation results align with the expectations of clinical experts, showing that features crucial for AF detection contribute heavily to the final decision. These features include R-R interval regularity, absence of the P-wave or presence of electrical activity in the isoelectric period. On the other hand, with local explanation, we analyze specific input signals and model outcomes. We present a comprehensive analysis of the network facing different conditions, whether the model has correctly classified the input signal or not. This enables a deeper understanding of the network's behavior, showing the most informative regions that trigger the classification decision and highlighting possible causes of misbehavior.

Machine Learning and the Future of Cardiovascular Care: JACC State-of-the-Art Review.

The role of physicians has always been to synthesize the data available to them to identify diagnostic patterns that guide treatment and follow response. Today, increasingly sophisticated machine learning algorithms may grow to support clinical experts in some of these tasks. Machine learning has the potential to benefit patients and cardiologists, but only if clinicians take an active role in bringing these new algorithms into practice. The aim of this review is to introduce clinicians who are not data science experts to key concepts in machine learning that will allow them to better understand the field and evaluate new literature and developments. The current published data in machine learning for cardiovascular disease is then summarized, using both a bibliometric survey, with code publicly available to enable similar analysis for any research topic of interest, and select case studies. Finally, several ways that clinicians can and must be involved in this emerging field are presented.