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Background: While universal screening for Lp(a; lipoprotein[a]) is increasingly recommended, <0.5% of patients undergo Lp(a) testing. Here, we assessed the feasibility of deploying Algorithmic Risk Inspection for Screening Elevated Lp(a; ARISE), a validated machine learning tool, to health system electronic health records to increase the yield of Lp(a) testing., Methods: We randomly sampled 100 000 patients from the Yale-New Haven Health System to evaluate the feasibility of ARISE deployment. We also evaluated Lp(a)-tested populations in the Yale-New Haven Health System (n=7981) and the Vanderbilt University Medical Center (n=10 635) to assess the association of ARISE scores with elevated Lp(a). To compare the representativeness of the Lp(a)-tested population, we included 456 815 participants from the UK Biobank and 23 280 from 3 US-based cohorts of Atherosclerosis Risk in Communities, Coronary Artery Risk Development in Young Adults, and Multi-Ethnic Study of Atherosclerosis., Results: Among 100 000 randomly selected Yale-New Haven Health System patients, 413 (0.4%) had undergone Lp(a) measurement. ARISE scores could be computed for 31 586 patients based on existing data, identifying 2376 (7.5%) patients with a high probability of elevated Lp(a). A positive ARISE score was associated with significantly higher odds of elevated Lp(a) in the Yale-New Haven Health System (odds ratio, 1.87 [95% CI, 1.65-2.12]) and the Vanderbilt University Medical Center (odds ratio, 1.41 [95% CI, 1.24-1.60]). The Lp(a)-tested population significantly differed from other study cohorts in terms of ARISE features., Conclusions: We demonstrate the feasibility of deployment of ARISE in US health systems to define the risk of elevated Lp(a), enabling a high-yield testing strategy. We also confirm the low adoption of Lp(a) testing, which is also being restricted to a highly selected population.

Background and Aims: Current heart failure (HF) risk stratification strategies require comprehensive clinical evaluation. In this study, artificial intelligence (AI) applied to electrocardiogram (ECG) images was examined as a strategy to predict HF risk., Methods: Across multinational cohorts in the Yale New Haven Health System (YNHHS), UK Biobank (UKB), and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), individuals without baseline HF were followed for the first HF hospitalization. An AI-ECG model that defines cross-sectional left ventricular systolic dysfunction from 12-lead ECG images was used, and its association with incident HF was evaluated. Discrimination was assessed using Harrell's C-statistic. Pooled cohort equations to prevent HF (PCP-HF) were used as a comparator., Results: Among 231 285 YNHHS patients, 4472 had primary HF hospitalizations over 4.5 years (inter-quartile range 2.5-6.6). In UKB and ELSA-Brasil, among 42 141 and 13 454 people, 46 and 31 developed HF over 3.1 (2.1-4.5) and 4.2 (3.7-4.5) years. A positive AI-ECG screen portended a 4- to 24-fold higher risk of new-onset HF [age-, sex-adjusted hazard ratio: YNHHS, 3.88 (95% confidence interval 3.63-4.14); UKB, 12.85 (6.87-24.02); ELSA-Brasil, 23.50 (11.09-49.81)]. The association was consistent after accounting for comorbidities and the competing risk of death. Higher probabilities were associated with progressively higher HF risk. Model discrimination was 0.718 in YNHHS, 0.769 in UKB, and 0.810 in ELSA-Brasil. In YNHHS and ELSA-Brasil, incorporating AI-ECG with PCP-HF yielded a significant improvement in discrimination over PCP-HF alone., Conclusions: An AI model applied to a single ECG image defined the risk of future HF, representing a digital biomarker for stratifying HF risk., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability. We aimed to examine an application of artificial intelligence (AI) to ECG images as a surrogate for imaging risk biomarkers and its association with early CTRCD., Methods: Across a US-based health system (2013-2023), we identified 1550 patients (aged, 60 [interquartile range, 51-69] years, 1223 [78.9%] women) without cardiomyopathy who received anthracyclines or trastuzumab for breast cancer or non-Hodgkin lymphoma and had ECG performed ≤12 months before treatment. We deployed a validated AI model of left ventricular systolic dysfunction to baseline ECG images and defined low-, intermediate-, and high-risk groups based on AI-ECG left ventricular systolic dysfunction probabilities of <0.01, 0.01 to 0.1, and ≥0.1 (positive screen), respectively. We explored the association with early CTRCD (new cardiomyopathy, heart failure, or left ventricular ejection fraction <50%), or left ventricular ejection fraction <40%, up to 12 months after treatment. In a mechanistic analysis, we assessed the association between global longitudinal strain and AI-ECG left ventricular systolic dysfunction probabilities in studies performed within 15 days of each other., Results: Among 1550 patients without known cardiomyopathy (median follow-up, 14.1 [interquartile range, 13.4-17.1] months), 83 (5.4%), 562 (36.3%), and 905 (58.4%) were classified as high, intermediate, and low risk, respectively, by baseline AI-ECG. A high-risk versus low-risk AI-ECG screen (≥0.1 versus <0.01) was associated with a 3.4-fold and 13.5-fold higher incidence of CTRCD (adjusted hazard ratio, 3.35 [95% CI, 2.25-4.99]) and left ventricular ejection fraction <40% (adjusted hazard ratio, 13.52 [95% CI, 5.06-36.10]), respectively. Post hoc analyses supported longitudinal increases in AI-ECG probabilities within 6 to 12 months of a CTRCD event. Among 1428 temporally linked echocardiograms and ECGs, AI-ECG left ventricular systolic dysfunction probabilities were associated with worse global longitudinal strain (global longitudinal strain, -19% [interquartile range, -21% to -17%] for probabilities <0.1, to -15% [interquartile range, -15% to -9%] for ≥0.5 [ P <0.001])., Conclusions: AI applied to baseline ECG images can stratify the risk of early CTRCD associated with anthracycline or trastuzumab exposure in the setting of breast cancer and non-Hodgkin lymphoma therapy., Competing Interests: Dr Khera is an Associate Editor of JAMA and receives research support, through Yale, from the Blavatnik Foundation, Bristol-Myers Squibb, Novo Nordisk, and BridgeBio. He is a coinventor of US Provisional Patent Applications 63/177,117, 63/428,569, 63/346,610, 63/484,426, 63/508,315, 63/580,137, 63/606,203, and 63/562,335, and a cofounder of Ensight-AI Inc and Evidence2Health LLC. Dr Oikonomou is an academic cofounder of Evidence2Health LLC, and has been a consultant for Ensight-AI Inc and Caristo Diagnostics Ltd. He is a coinventor in patent applications (US17/720,068, 63/619,241, 63/177,117, 63/580,137, 63/606,203, 63/562,335, US11948230B2, and US20210374951A1) and has received royalty fees from technology licensed through the University of Oxford, outside the submitted work. V. Sangha is a coinventor of 63/346,610 and 63/484,426, and a cofounder of Ensight-AI, Inc. Dr Krumholz works under contract with the Centers for Medicare and Medicaid Services to support quality measurement programs, was a recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold and Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the cofounder of Hugo Health, a personal health information platform, and cofounder of Refactor Health, a health care AI-augmented data management company, and Ensight-AI Inc. The other authors report no conflicts.

Background: The lack of automated tools for measuring care quality limits the implementation of a national program to assess guideline-directed care in heart failure with reduced ejection fraction (HFrEF)., Objectives: The authors aimed to automate the identification of patients with HFrEF at hospital discharge, an opportunity to evaluate and improve the quality of care., Methods: The authors developed a novel deep-learning language model for identifying patients with HFrEF from discharge summaries of hospitalizations with heart failure at Yale New Haven Hospital during 2015 to 2019. HFrEF was defined by left ventricular ejection fraction <40% on antecedent echocardiography. The authors externally validated the model at Northwestern Medicine, community hospitals of Yale, and the MIMIC-III (Medical Information Mart for Intensive Care III) database., Results: A total of 13,251 notes from 5,392 unique individuals (age 73 ± 14 years, 48% women), including 2,487 patients with HFrEF (46.1%), were used for model development (train/held-out: 70%/30%). The model achieved an area under receiver-operating characteristic curve (AUROC) of 0.97 and area under precision recall curve (AUPRC) of 0.97 in detecting HFrEF on the held-out set. The model had high performance in identifying HFrEF with AUROC = 0.94 and AUPRC = 0.91 on 19,242 notes from Northwestern Medicine, AUROC = 0.95 and AUPRC = 0.96 on 139 manually abstracted notes from Yale community hospitals, and AUROC = 0.91 and AUPRC = 0.92 on 146 manually reviewed notes from MIMIC-III. Model-based predictions of HFrEF corresponded to a net reclassification improvement of 60.2% ± 1.9% compared with diagnosis codes (P < 0.001)., Conclusions: The authors developed a language model that identifies HFrEF from clinical notes with high precision and accuracy, representing a key element in automating quality assessment for individuals with HFrEF., Competing Interests: Funding Support and Author Disclosures This study was supported by research funding awarded to Dr Khera by the Yale School of Medicine and grant support from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under the award K23HL153775. Dr Ahmad is a consultant for Sanofi Aventis, Amgen, and Cytokinetics; and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. Dr Nadkarni has consultancy agreements with AstraZeneca, BioVie, GLG Consulting, Pensieve Health, Reata, Renalytix, Siemens Healthineers and Variant Bio; has received research funding from Goldfinch Bio, and Renalytix; has received honoraria from AstraZeneca, BioVie, Lexicon, Daiichi Sankyo, Meanrini Health, and Reata; has patents or royalties with Renalytix; owns equity and stock options in Pensieve Health and Renalytix as a scientific cofounder; owns equity in Verici Dx; has received financial compensation as a scientific board member and advisor to Renalytix; has served on the advisory board of Neurona Health; and has served in an advisory or leadership role for Pensieve Health and Renalytix. Dr Ahmad has received grants from the Agency for Healthcare Research and Quality, NIH/NHLBI, and American Heart Association; and has received personal fees from Teladoc, Livongo, and Pfizer, outside of the submitted work. Dr Krumholz works under contract with the Centers for Medicare and Medicaid Services to support quality measurement programs; was a recipient of a research grant from Johnson and Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold and Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the cofounder of Hugo Health, a personal health information platform, and cofounder of Refactor Health, a health care AI-augmented data management company. Dr Khera is an Associate Editor of JAMA; receives support from the NHLBI of the NIH (under awards R01HL167858 and K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060); has received research support, through Yale, from Bristol Myers Squibb, Novo Nordisk, and BridgeBio; is a coinventor of U.S. Pending Patent Applications 63/562,335, 63/177,117, 63/428,569, 63/346,610, 63/484,426, 63/508,315, and 63/606,203; and is a co-founder of Ensight-AI, Inc and Evidence2Health, health platforms to improve cardiovascular diagnosis and evidence-based cardiovascular care. Dr Nargesi has received funding from the NHLBI under award number T32HL007604. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025. Published by Elsevier Inc.)

Background: Identifying structural heart diseases (SHDs) early can change the course of the disease, but their diagnosis requires cardiac imaging, which is limited in accessibility., Objective: To leverage images of 12-lead ECGs for automated detection and prediction of multiple SHDs using an ensemble deep learning approach., Methods: We developed a series of convolutional neural network models for detecting a range of individual SHDs from images of ECGs with SHDs defined by transthoracic echocardiograms (TTEs) performed within 30 days of the ECG at the Yale New Haven Hospital (YNHH). SHDs were defined as LV ejection fraction <40%, moderate-to-severe left-sided valvular disease (aortic/mitral stenosis or regurgitation), or severe left ventricular hypertrophy (IVSd > 1.5cm and diastolic dysfunction). We developed an ensemble XGBoost model, PRESENT-SHD, as a composite screen across all SHDs. We validated PRESENT-SHD at 4 US hospitals and the prospective, population-based Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), with concurrent protocolized ECGs and TTEs. We also used PRESENT-SHD for risk stratification of new-onset SHD or heart failure (HF) in clinical cohorts and the population-based UK Biobank (UKB)., Results: The models were developed using 261,228 ECGs from 93,693 YNHH patients and evaluated on a single ECG from 11,023 individuals at YNHH (19% with SHD), 44,591 across external hospitals (20-27% with SHD), and 3,014 in the ELSA-Brasil (3% with SHD). In the held-out test set, PRESENT-SHD demonstrated an AUROC of 0.886 (0.877-894), 90% sensitivity, and 66% specificity. At hospital-based sites, PRESENT-SHD had AUROCs ranging from 0.854-0.900, with sensitivities and specificities of 93-96% and 51-56%, respectively. The model generalized well to ELSA-Brasil (AUROC, 0.853 [0.811-0.897], 88% sensitivity, 62% specificity). PRESENT-SHD demonstrated consistent performance across demographic subgroups, novel ECG formats, and smartphone photographs of ECGs from monitors and printouts. A positive PRESENT-SHD screen portended a 2- to 4-fold higher risk of new-onset SHD/HF, independent of demographics, comorbidities, and the competing risk of death across clinical sites and UKB, with high predictive discrimination., Conclusion: We developed and validated PRESENT-SHD, an AI-ECG tool identifying a range of SHD using images of 12-lead ECGs, representing a robust, scalable, and accessible modality for automated SHD screening and risk stratification., Competing Interests: Dr. Khera is an Associate Editor of JAMA. Dr. Khera and Mr. Sangha are the coinventors of U.S. Provisional Patent Application No. 63/346,610, “Articles and methods for format-independent detection of hidden cardiovascular disease from printed electrocardiographic images using deep learning” and are co-founders of Ensight-AI. Dr. Khera receives support from the National Institutes of Health (under awards R01AG089981, R01HL167858, and K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060). He receives support from the Blavatnik Foundation through the Blavatnik Fund for Innovation at Yale. He also receives research support, through Yale, from Bristol-Myers Squibb, BridgeBio, and Novo Nordisk. In addition to 63/346,610, Dr. Khera is a coinventor of U.S. Pending Patent Applications WO2023230345A1, US20220336048A1, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335. Dr. Khera and Dr. Oikonomou are co-founders of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. Dr. Oikonomou has been a consultant for Caristo Diagnostics Ltd and Ensight-AI Inc, and has received royalty fees from technology licensed through the University of Oxford, outside the submitted work. Dr. Krumholz is the Editor-in-Chief of JACC. Dr. Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs. He is associated with research contracts through Yale University from Janssen, Kenvue, and Pfizer. In the past three years, Dr. Krumholz received options for Element Science and Identifeye and payments from F-Prime for advisory roles. He is a co-founder of and holds equity in Hugo Health, Refactor Health, and Ensight-AI. Dr. Ribeiro is supported in part by the National Council for Scientific and Technological Development - CNPq (grants 465518/2014-1, 310790/2021-2, 409604/2022-4 e 445011/2023-8). Dr. Brant is supported in part by CNPq (307329/2022-4). All other authors declare no competing interests.

Importance: Despite the availability of disease-modifying therapies, scalable strategies for heart failure (HF) risk stratification remain elusive. Portable devices capable of recording single-lead electrocardiograms (ECGs) can enable large-scale community-based risk assessment., Objective: To evaluate an artificial intelligence (AI) algorithm to predict HF risk from noisy single-lead ECGs., Design: Multicohort study., Setting: Retrospective cohort of individuals with outpatient ECGs in the integrated Yale New Haven Health System (YNHHS) and prospective population-based cohorts of UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)., Participants: Individuals without HF at baseline., Exposures: AI-ECG-defined risk of left ventricular systolic dysfunction (LVSD)., Main Outcomes and Measures: Among individuals with ECGs, we isolated lead I ECGs and deployed a noise-adapted AI-ECG model trained to identify LVSD. We evaluated the association of the model probability with new-onset HF, defined as the first HF hospitalization. We compared the discrimination of AI-ECG against two risk scores for new-onset HF (PCP-HF and PREVENT equations) using Harrel's C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)., Results: There were 192,667 YNHHS patients (age 56 years [IQR, 41-69], 112,082 women [58%]), 42,141 UKB participants (65 years [59-71], 21,795 women [52%]), and 13,454 ELSA-Brasil participants (56 years [41-69], 7,348 women [55%]) with baseline ECGs. A total of 3,697 developed HF in YNHHS over 4.6 years (2.8-6.6), 46 in UKB over 3.1 years (2.1-4.5), and 31 in ELSA-Brasil over 4.2 years (3.7-4.5). A positive AI-ECG screen was associated with a 3- to 7-fold higher risk for HF, and each 0.1 increment in the model probability portended a 27-65% higher hazard across cohorts, independent of age, sex, comorbidities, and competing risk of death. AI-ECG's discrimination for new-onset HF was 0.725 in YNHHS, 0.792 in UKB, and 0.833 in ELSA-Brasil. Across cohorts, incorporating AI-ECG predictions in addition to PCP-HF and PREVENT equations resulted in improved Harrel's C-statistic (Δ PCP-HF =0.112-0.114; Δ PREVENT =0.080-0.101). AI-ECG had IDI of 0.094-0.238 and 0.090-0.192, and NRI of 15.8%-48.8% and 12.8%-36.3%, vs. PCP-HF and PREVENT, respectively., Conclusions and Relevance: Across multinational cohorts, a noise-adapted AI model defined HF risk using lead I ECGs, suggesting a potential portable and wearable device-based HF risk-stratification strategy., Competing Interests: Dr. Khera is an Associate Editor of JAMA. Dr. Khera and Mr. Sangha are the coinventors of U.S. Provisional Patent Application No. 63/346,610, “Articles and methods for format-independent detection of hidden cardiovascular disease from printed electrocardiographic images using deep learning” and are co-founders of Ensight-AI. Dr. Khera receives support the National Institutes of Health (under awards R01AG089981, R01HL167858, and K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060). He receives support from the Blavatnik Foundation through the Blavatnik Fund for Innovation at Yale. He also receives research support, through Yale, from Bristol-Myers Squibb, BridgeBio, and Novo Nordisk. In addition to 63/346,610, Dr. Khera is a coinventor of U.S. Pending Patent Applications WO2023230345A1, US20220336048A1, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335. Dr. Khera and Dr. Oikonomou are co-founders of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. Dr. Oikonomou is a co-inventor of the U.S. Patent Applications 63/508,315 & 63/177,117 and has been a consultant to Caristo Diagnostics Ltd (all outside the current work). Dr. Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs. He is associated with research contracts through Yale University from Janssen, Kenvue, and Pfizer. In the past three years, Dr. Krumholz received options for Element Science and Identifeye and payments from F-Prime for advisory roles. He is a co-founder of and holds equity in Hugo Health, Refactor Health, and Ensight-AI. Dr. Ribeiro is supported in part by the National Council for Scientific and Technological Development - CNPq (grants 465518/2014-1, 310790/2021-2, 409604/2022-4 e 445011/2023-8). Dr. Brant is supported in part by CNPq (307329/2022-4). Dr. Asselbergs is supported by Heart4Data, which received funding from the Dutch Heart Foundation and ZonMw (2021-B015), and UCL Hospitals NIHR Biomedical Research Centre.

Artificial intelligence-enhanced electrocardiography (AI-ECG) can identify hypertrophic cardiomyopathy (HCM) on 12-lead ECGs and offers a novel way to monitor treatment response. Although the surgical or percutaneous reduction of the interventricular septum (SRT) represented initial HCM therapies, mavacamten offers an oral alternative. We aimed to assess the use of AI-ECG as a strategy to evaluate biologic responses to SRT and mavacamten. We applied an AI-ECG model for HCM detection to electrocardiography images from patients who underwent SRT across 3 sites: Yale New Haven Health System (YNHHS), Cleveland Clinic Foundation (CCF), and Atlantic Health System (AHS) and to electrocardiography images from patients receiving mavacamten at YNHHS. A total of 70 patients underwent SRT at YNHHS, 100 at CCF, and 145 at AHS. At YNHHS, there was no significant change in the AI-ECG HCM score before versus after SRT (before SRT: median 0.55 [interquartile range 0.24 to 0.77] vs after SRT: 0.59 [0.40 to 0.75]). The AI-ECG HCM scores also did not improve after SRT at CCF (0.61 [0.32 to 0.79] vs 0.69 [0.52 to 0.79]) and AHS (0.52 [0.35 to 0.69] vs 0.61 [0.49 to 0.70]). Of the 36 YNHHS patients on mavacamten therapy, the median AI-ECG score before starting mavacamten was 0.41 (0.22 to 0.77), which decreased significantly to 0.28 (0.11 to 0.50, p <0.001 by Wilcoxon signed-rank test) at the end of a median follow-up period of 237 days. In conclusion, we observed a lack of improvement in AI-based HCM score with SRT, in contrast to a significant decrease with mavacamten. Our approach suggests the potential role of AI-ECG for serial point-of-care monitoring of pathophysiologic improvement after medical therapy in HCM using ECG images., Competing Interests: Declaration of competing interest Mr. Sangha and Dr. Khera are the coinventors of US Provisional Patent Application No. 63/346,610, “Articles and methods for format-independent detection of hidden cardiovascular disease from printed electrocardiographic images using deep learning.” Dr. Khera receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under awards R01AG089981, R01HL167858, and K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060). He receives support from the Blavatnik Foundation through the Blavatnik fund for Innovation at Yale. He also receives research support, through Yale, from Bristol-Myers Squibb, Novo Nordisk, and BridgeBio. He is an Associate Editor at JAMA. In addition to 63/346,610, Dr. Khera is a coinventor of US Provisional Patent Applications 63/177,117, 63/428,569, and 63/484,426. Dr. Khera and Dr. Oikonomou are cofounders of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. Dr. Oikonomou is a coinventor of the US Patent Applications 63/508,315 & 63/177,117 and has served as a consultant to Caristo Diagnostics Ltd (all outside the current work). Dr. Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs, was a recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the co-founder of Hugo Health, a personal health information platform; and co-founder of Refactor Health, a health care AI-augmented data management company. Mr. Sangha, Dr. Krumholz and Dr. Khera are cofounders of Ensight-AI, Inc., a Yale-backed startup focusing on cardiovascular diagnostics. Dr. Desai acknowledges the Haslam family–endowed chair in cardiovascular medicine and receives philanthropic support from the Holekamp and Stinson family. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Serial functional status assessments are critical to heart failure (HF) management but are often described narratively in documentation, limiting their use in quality improvement or patient selection for clinical trials., Objective: To develop and validate a deep learning natural language processing (NLP) strategy for extracting functional status assessments from unstructured clinical documentation., Design, Setting, and Participants: This diagnostic study used electronic health record data collected from January 1, 2013, through June 30, 2022, from patients diagnosed with HF seeking outpatient care within 3 large practice networks in Connecticut (Yale New Haven Hospital [YNHH], Northeast Medical Group [NMG], and Greenwich Hospital [GH]). Expert-annotated notes were used for NLP model development and validation. Data were analyzed from February to April 2024., Exposures: Development and validation of NLP models to detect explicit New York Heart Association (NYHA) classification, HF symptoms during activity or rest, and frequency of functional status assessments., Main Outcomes and Measures: Outcomes of interest were model performance metrics, including area under the receiver operating characteristic curve (AUROC), and frequency of NYHA class documentation and HF symptom descriptions in unannotated notes., Results: This study included 34 070 patients with HF (mean [SD] age 76.1 [12.6] years; 17 728 [52.0]% female). Among 3000 expert-annotated notes (2000 from YNHH and 500 each from NMG and GH), 374 notes (12.4%) mentioned NYHA class and 1190 notes (39.7%) described HF symptoms. The NYHA class detection model achieved a class-weighted AUROC of 0.99 (95% CI, 0.98-1.00) at YNHH, the development site. At the 2 validation sites, NMG and GH, the model achieved class-weighted AUROCs of 0.98 (95% CI, 0.96-1.00) and 0.98 (95% CI, 0.92-1.00), respectively. The model for detecting activity- or rest-related symptoms achieved an AUROC of 0.94 (95% CI, 0.89-0.98) at YNHH, 0.94 (95% CI, 0.91-0.97) at NMG, and 0.95 (95% CI, 0.92-0.99) at GH. Deploying the NYHA model among 182 308 unannotated notes from the 3 sites identified 23 830 (13.1%) notes with NYHA mentions, specifically 10 913 notes (6.0%) with class I, 12 034 notes (6.6%) with classes II or III, and 883 notes (0.5%) with class IV. An additional 19 730 encounters (10.8%) could be classified into functional status groups based on activity- or rest-related symptoms, resulting in a total of 43 560 medical notes (23.9%) categorized by NYHA, an 83% increase compared with explicit mentions alone., Conclusions and Relevance: In this diagnostic study of 34 070 patients with HF, the NLP approach accurately extracted a patient's NYHA symptom class and activity- or rest-related HF symptoms from clinical notes, enhancing the ability to track optimal care delivery and identify patients eligible for clinical trial participation from unstructured documentation.

Background: Rich data in cardiovascular diagnostic testing are often sequestered in unstructured reports, with the necessity of manual abstraction limiting their use in real-time applications in patient care and research., Methods: We developed a two-step process that sequentially deploys generative and interpretative large language models (LLMs; Llama2 70b and Llama2 13b). Using a Llama2 70b model, we generated varying formats of transthoracic echocardiogram (TTE) reports from 3,000 real-world echo reports with paired structured elements, leveraging temporal changes in reporting formats to define the variations. Subsequently, we fine-tuned Llama2 13b using sequentially larger batches of generated echo reports as inputs, to extract data from free-text narratives across 18 clinically relevant echocardiographic fields. This was set up as a prompt-based supervised training task. We evaluated the fine-tuned Llama2 13b model, HeartDx-LM, on several distinct echocardiographic datasets: (i) reports across the different time periods and formats at Yale New Haven Health System (YNHHS), (ii) the Medical Information Mart for Intensive Care (MIMIC) III dataset, and (iii) the MIMIC IV dataset. We used the accuracy of extracted fields and Cohen's Kappa as the metrics and have publicly released the HeartDX-LM model., Results: The HeartDX-LM model was trained on randomly selected 2,000 synthetic echo reports with varying formats and paired structured labels, with a wide range of clinical findings. We identified a lower threshold of 500 annotated reports required for fine-tuning Llama2 13b to achieve stable and consistent performance. At YNHHS, the HeartDx-LM model accurately extracted 69,144 out of 70,032 values (98.7%) across 18 clinical fields from unstructured reports in the test set from contemporary records where paired structured data were also available. In older echo reports where only unstructured reports were available, the model achieved 87.1% accuracy against expert annotations for the same 18 fields for a random sample of 100 reports. Similarly, in expert-annotated external validation sets from MIMIC-IV and MIMIC-III, HeartDx-LM correctly extracted 201 out of 220 available values (91.3%) and 615 out of 707 available values (87.9%), respectively, from 100 randomly chosen and expert annotated echo reports from each set., Conclusion: We developed a novel method using paired large and moderate-sized LLMs to automate the extraction of unstructured echocardiographic reports into tabular datasets. Our approach represents a scalable strategy that transforms unstructured reports into computable elements that can be leveraged to improve cardiovascular care quality and enable research., Competing Interests: Dr. Khera is an Associate Editor of JAMA and is a co-founder of Ensight-AI. Dr. Khera receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under awards R01HL167858 and K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060). He receives support from the Blavatnik Foundation through the Blavatnik Fund for Innovation at Yale. He also receives research support, through Yale, from Bristol-Myers Squibb, BridgeBio, and Novo Nordisk. In addition to 63/346,610, Dr. Khera is a coinventor of U.S. Pending Patent Applications WO2023230345A1, US20220336048A1, 63/484,426, 63/508,315, 63/580,137, 63/619,241, 63/346,610, 63/562,335 and 18/813,882. Dr. Khera, Dr. Oikonomou and Mr. Vasisht Shankar are co-inventors of the US patent application 63/606,203. Dr. Khera and Dr. Oikonomou are co-founders of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. Dr. Oikonomou receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award F32HL170592). He is a co-inventor of the U.S. Patent Applications 18/813,882, 17/720,068, 63/619,241, 63/177,117, 63/580,137, 63/606,203, 63/562,335, US11948230B2 , US20210374951A1. He has been a consultant for Caristo Diagnostics Ltd and Ensight-AI Inc, and has received royalty fees from technology licensed through the University of Oxford.. Mr. Vasisht Shankar works as a data scientist at Evidence2Health (outside the current work). Dr. Nadkarni is a founder of Renalytix, Pensieve, and Verici and provides consultancy services to AstraZeneca, Reata, Renalytix, and Pensieve. He also has equity in Renalytix, Pensieve, and Verici.

Background and Aims: AI-enhanced 12-lead ECG can detect a range of structural heart diseases (SHDs) but has a limited role in community-based screening. We developed and externally validated a noise-resilient single-lead AI-ECG algorithm that can detect SHD and predict the risk of their development using wearable/portable devices., Methods: Using 266,740 ECGs from 99,205 patients with paired echocardiographic data at Yale New Haven Hospital, we developed ADAPT-HEART, a noise-resilient, deep-learning algorithm, to detect SHD using lead I ECG. SHD was defined as a composite of LVEF<40%, moderate or severe left-sided valvular disease, and severe LVH. ADAPT-HEART was validated in four community hospitals in the US, and the population-based cohort of ELSA-Brasil. We assessed the model's performance as a predictive biomarker among those without baseline SHD across hospital-based sites and the UK Biobank., Results: The development population had a median age of 66 [IQR, 54-77] years and included 49,947 (50.3%) women, with 18,896 (19.0%) having any SHD. ADAPT-HEART had an AUROC of 0.879 (95% CI, 0.870-0.888) with good calibration for detecting SHD in the test set, and consistent performance in hospital-based external sites (AUROC: 0.852-0.891) and ELSA-Brasil (AUROC: 0.859). Among those without baseline SHD, high vs. low ADAPT-HEART probability conferred a 2.8- to 5.7-fold increase in the risk of future SHD across data sources (all P<0.05)., Conclusions: We propose a novel model that detects and predicts a range of SHDs from noisy single-lead ECGs obtainable on portable/wearable devices, providing a scalable strategy for community-based screening and risk stratification for SHD.

Background: Assessment of stroke risk in patients with atrial fibrillation (AF) is crucial for guiding anticoagulation therapy. CHA 2 DS 2 -VASc is a widely used score for defining this risk, but current assessments rely on manual calculation by clinicians or approximations from structured EHR data elements. Unstructured clinical notes contain rich information that could enhance risk assessment. We developed and validated a Retrieval-Augmented Generation (RAG) approach to extract CHA 2 DS 2 -VASc risk factors from unstructured notes in patients with AF., Methods: We employed a RAG architecture paired with the large language model, Llama3.1, to extract features relevant to CHA 2 DS 2 -VASc scores from unstructured notes. The model was deployed on a random set of 1,000 clinical notes (934 AF patients) from Yale New Haven Health System (YNHHS). To establish a gold standard, 2 clinicians manually reviewed and labeled CHA 2 DS 2 -VASc risk factors in a random subset of 200 notes. The CHA 2 DS 2 -VASc scores were calculated for each patient using structured data alone and by incorporating risk factors identified with RAG. We assessed performance across risk factors using macro-averaged area under the receiver operating characteristic (AUROC). For external validation, we utilized 100 manually labeled clinical notes from the MIMIC-IV database., Results: The RAG model demonstrated robust performance in extracting risk factors from clinical notes. In the 1000 clinical notes, RAG identified several risk factors more frequently than structured elements, including hypertension (82.4% vs 26.2%), stroke/TIA (62.9% vs 45.5%), vascular disease (83.4% vs 56.6%), and diabetes (84.1% vs 47.2%). In the 200 expert-annotated notes, the RAG approach achieved high performance for various risk factors, with AUROCs ranging from 0.96 to 0.98 for hypertension, diabetes, and age ≥75 years. Incorporating risk factors identified by RAG increased CHA 2 DS 2 -VASc scores compared with using structured data alone., Conclusion: An LLM-optimized RAG can accurately extract CHA 2 DS 2 -VASc risk factors from unstructured clinical notes in AF patients. This approach can enable computable risk assessment and guide appropriate anticoagulation therapy.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials., Objectives: The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM., Methods: Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis., Results: Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13])., Conclusions: In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD., Competing Interests: Funding Support and Author Disclosures This study was partially funded through National Institutes of Health grants R01 HL167858, K23 HL153775, R01 LM006910, R01 HG006139, and R01 HL169954 and the U.S. Department of Veterans Affairs under the research priority to “Put VA Data to Work for Veterans” (VA ORD 22-D4V). The funders had no role in the design and conduct of the protocol; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Khera is an associate editor at JAMA; and has received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (awards R01 HL167858 and K23 HL153775) and the Doris Duke Charitable Foundation (award 2022060); has received research support, through Yale University, from Bristol Myers Squibb, Novo Nordisk, and BridgeBio; is a coinventor of U.S. provisional patent applications WO2023230345A1, US20220336048A1, 63/346,610, 63/428,569, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335, unrelated to the present work; and is a cofounder of Evidence2Health and Ensight-AI, precision health platforms to improve evidence-based cardiovascular care and cardiovascular diagnostics. Dr DuVall has received grants from Alnylam Pharmaceuticals, AstraZeneca Pharmaceuticals, Biodesix, Celgene, Cerner Enviza, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis International, and Parexel International through the University of Utah or the Western Institute for Veteran Research (outside the submitted work). Dr Man has received support from the C.W. Maplethorpe Fellowship, the National Institute of Health Research, European Commission Framework Horizon 2020, the Hong Kong Research Grant Council, and the Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the submitted work). Dr Morales is supported by a Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). In the past 3 years, Dr Krumholz has received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, the Arnold and Porter Law Firm, and the Martin/Baughman Law Firm; is a cofounder of Refactor Health, HugoHealth, and Ensight-AI; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare and Medicaid Services and, through Yale University, from Johnson & Johnson. Dr You is chief technology officer of PHI Digital Healthcare. Dr Ross has received research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (grant U01 FD005938), from the Agency for Healthcare Research and Quality (grant R01 HS022882), and from Arnold Ventures; has received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology and from the National Heart, Lung, and Blood Institute of the National Institutes of Health (grants R01 HS025164 and R01 HL144644); and was an expert witness at the request of the relator’s attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled September 2022. Dr Thangaraj is a coinventor on provisional patent 63/606,203, unrelated to the present work, and is funded by grant 5T32 HL155000-03. Ms Blacketer, Dr Ostropolets, and Dr Ryan are employees of Johnson & Johnson. Dr Schuemie is an employee and shareholder of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Aims: Despite notable population differences in high-income and low- and middle-income countries (LMICs), national guidelines in LMICs often recommend using US-based cardiovascular disease (CVD) risk scores for treatment decisions. We examined the performance of widely used international CVD risk scores within the largest Brazilian community-based cohort study (Brazilian Longitudinal Study of Adult Health, ELSA-Brasil)., Methods: All adults 40-75 years from ELSA-Brasil (2008-2013) without prior CVD who were followed for incident, adjudicated CVD events (fatal and non-fatal MI, stroke, or coronary heart disease death). We evaluated 5 scores-Framingham General Risk (FGR), Pooled Cohort Equations (PCEs), WHO CVD score, Globorisk-LAC and the Systematic Coronary Risk Evaluation 2 score (SCORE-2). We assessed their discrimination using the area under the receiver operating characteristic curve (AUC) and calibration with predicted-to-observed risk (P/O) ratios-overall and by sex/race groups., Results: There were 12 155 individuals (53.0±8.2 years, 55.3% female) who suffered 149 incident CVD events. All scores had a model AUC>0.7 overall and for most age/sex groups, except for white women, where AUC was <0.6 for all scores, with higher overestimation in this subgroup. All risk scores overestimated CVD risk with 32%-170% overestimation across scores. PCE and FGR had the highest overestimation (P/O ratio: 2.74 (95% CI 2.42 to 3.06)) and 2.61 (95% CI 1.79 to 3.43)) and the recalibrated WHO score had the best calibration (P/O ratio: 1.32 (95% CI 1.12 to 1.48))., Conclusion: In a large prospective cohort from Brazil, we found that widely accepted CVD risk scores overestimate risk by over twofold, and have poor risk discrimination particularly among Brazilian women. Our work highlights the value of risk stratification strategies tailored to the unique populations and risks of LMICs., Competing Interests: Competing interests: RK is an Associate Editor at JAMA. In addition to the funding listed above, he also receives research support, through Yale, from Bristol-Myers Squibb, Novo Nordisk and BridgeBio. He is a coinventor of Pending Patent Applications WO2023230345A1, US20220336048A1, 63/346 610, 63/484 426, 63/508 315, 63/580 137, 63/606 203, 63/619 241 and 63/562 335, unrelated to current work. He is also a co-founder of Evidence2Health and Ensight-AI, both representing precision health platforms to improve evidence-based cardiovascular care. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Portable devices capable of electrocardiogram (ECG) acquisition have the potential to enhance structural heart disease (SHD) management by enabling early detection through artificial intelligence-ECG (AI-ECG) algorithms. However, the performance of these AI algorithms for identifying SHD in a real-world screening setting is unknown. To address this gap, we aim to evaluate the validity of our wearable-adapted AI algorithm, which has been previously developed and validated for detecting SHD from single-lead portable ECGs in patients undergoing routine echocardiograms in the Yale New Haven Hospital (YNHH)., Research Methods and Analysis: This is the protocol for a cross-sectional study in the echocardiographic laboratories of YNHH. The study will enroll 585 patients referred for outpatient transthoracic echocardiogram (TTE) as part of their routine clinical care. Patients expressing interest in participating in the study will undergo a screening interview, followed by enrollment upon meeting eligibility criteria and providing informed consent. During their routine visit, patients will undergo a 1-lead ECG with two devices - one with an Apple Watch and the second with another portable 1-lead ECG device. With participant consent, these 1-lead ECG data will be linked to participant demographic and clinical data recorded in the YNHH electronic health records (EHR). The study will assess the performance of the AI-ECG algorithm in identifying SHD, including left ventricular systolic dysfunction (LVSD), valvular disease and severe left ventricular hypertrophy (LVH), by comparing the algorithm's results with data obtained from TTE, which is the established gold standard for diagnosing SHD., Ethics and Dissemination: All patient EHR data required for assessing eligibility and conducting the AI-ECG will be accessed through secure servers approved for protected health information. Data will be maintained on secure, encrypted servers for a minimum of five years after the publication of our findings in a peer-reviewed journal, and any unanticipated adverse events or risks will be reported by the principal investigator to the Yale Institutional Review Board, which has reviewed and approved this protocol (Protocol Number: 2000035532).

Importance: Randomized clinical trials (RCTs) are the standard for defining an evidence-based approach to managing disease, but their generalizability to real-world patients remains challenging to quantify., Objective: To develop a multidimensional patient variable mapping algorithm to quantify the similarity and representation of electronic health record (EHR) patients corresponding to an RCT and estimate the putative treatment effects in real-world settings based on individual treatment effects observed in an RCT., Design: A retrospective analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT; 2006-2012) and a multi-hospital patient cohort from the electronic health record (EHR) in the Yale New Haven Hospital System (YNHHS; 2015-2023)., Setting: A multicenter international RCT (TOPCAT) and multi-hospital patient cohort (YNHHS)., Participants: All TOPCAT participants and patients with heart failure with preserved ejection fraction (HFpEF) and ≥1 hospitalization within YNHHS., Exposures: 63 pre-randomization characteristics measured across the TOPCAT and YNNHS cohorts., Main Outcomes and Measures: Real-world generalizability of the RCT TOPCAT using a multidimensional phenotypic distance metric between TOPCAT and YNHHS cohorts. Estimation of the individualized treatment effect of spironolactone use on all-cause mortality within the YNHHS cohort based on phenotypic distance from the TOPCAT cohort., Results: There were 3,445 patients in TOPCAT and 11,712 HFpEF patients across five hospital sites. Across the 63 TOPCAT variables mapped by clinicians to the EHR, there were larger differences between TOPCAT and each of the 5 EHR sites (median SMD 0.200, IQR 0.037-0.410) than between the 5 EHR sites (median SMD 0.062, IQR 0.010-0.130). The synthesis of these differences across covariates using our multidimensional similarity score also suggested substantial phenotypic dissimilarity between the TOPCAT and EHR cohorts. By phenotypic distance, a majority (55%) of TOPCAT participants were closer to each other than any individual EHR patient. Using a TOPCAT-derived model of individualized treatment benefit from spironolactone, those predicted to derive benefit and receiving spironolactone in the EHR cohorts had substantially better outcomes compared with predicted benefit and not receiving the medication (HR 0.74, 95% CI 0.62-0.89)., Conclusions and Relevance: We propose a novel approach to evaluating the real-world representativeness of RCT participants against corresponding patients in the EHR across the full multidimensional spectrum of the represented phenotypes. This enables the evaluation of the implications of RCTs for real-world patients., Key Points: Question: How can we examine the multi-dimensional generalizability of randomized clinical trials (RCT) to real-world patient populations? Findings: We demonstrate a novel phenotypic distance metric comparing an RCT to real-world populations in a large multicenter RCT of heart failure patients and the corresponding patients in multisite electronic health records (EHRs). Across 63 pre-randomization characteristics, pairwise assessments of members of the RCT and EHR cohorts were more discordant from each other than between members of the EHR cohort (median standardized mean difference 0.200 [0.037-0.410] vs 0.062 [0.010-0.130]), with a majority (55%) of RCT participants closer to each other than any individual EHR patient. The approach also enabled the quantification of expected real world outcomes based on effects observed in the RCT. Meaning: A multidimensional phenotypic distance metric quantifies the generalizability of RCTs to a given population while also offering an avenue to examine expected real-world patient outcomes based on treatment effects observed in the RCT.

Elevated lipoprotein (a) (Lp(a)) is associated with premature atherosclerotic cardiovascular disease. However, fewer than 0.5% of individuals undergo Lp(a) testing, limiting the evaluation and use of novel targeted therapeutics currently under development. Here we describe the development of a machine learning model for targeted screening for elevated Lp(a) (≥150 nmol l -1 ) in the UK Biobank (N = 456,815), the largest cohort with protocolized Lp(a) testing. We externally validated the model in 3 large cohort studies, ARIC (N = 14,484), CARDIA (N = 4,124) and MESA (N = 4,672). The model, Algorithmic Risk Inspection for Screening Elevated Lp(a) (ARISE), reduced the number needed to test to find one individual with elevated Lp(a) by up to 67.3%, based on the probability threshold, with consistent performance across external validation cohorts. ARISE could be used to optimize screening for elevated Lp(a) using commonly available clinical features, with the potential for its deployment in electronic health records to enhance the yield of Lp(a) testing in real-world settings., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: An algorithmic strategy for anatomical vs. functional testing in suspected coronary artery disease (CAD) (Anatomical vs. Stress teSting decIsion Support Tool; ASSIST) is associated with better outcomes than random selection. However, in the real world, this decision is rarely random. We explored the agreement between a provider-driven vs. simulated algorithmic approach to cardiac testing and its association with outcomes across multinational cohorts., Methods and Results: In two cohorts of functional vs. anatomical testing in a US hospital health system [Yale; 2013-2023; n = 130 196 (97.0%) vs. n = 4020 (3.0%), respectively], and the UK Biobank [ n = 3320 (85.1%) vs. n = 581 (14.9%), respectively], we examined outcomes stratified by agreement between the real-world and ASSIST-recommended strategies. Younger age, female sex, Black race, and diabetes history were independently associated with lower odds of ASSIST-aligned testing. Over a median of 4.9 (interquartile range [IQR]: 2.4-7.1) and 5.4 (IQR: 2.6-8.8) years, referral to the ASSIST-recommended strategy was associated with a lower risk of acute myocardial infarction or death (hazard ratio adjusted : 0.81, 95% confidence interval [CI] 0.77-0.85, P < 0.001 and 0.74 [95% CI 0.60-0.90], P = 0.003, respectively), an effect that remained significant across years, test types, and risk profiles. In post hoc analyses of anatomical-first testing in the Prospective Multicentre Imaging Study for Evaluation of Chest Pain (PROMISE) trial, alignment with ASSIST was independently associated with a 17% and 30% higher risk of detecting CAD in any vessel or the left main artery/proximal left anterior descending coronary artery, respectively., Conclusion: In cohorts where historical practices largely favour functional testing, alignment with an algorithmic approach to cardiac testing defined by ASSIST was associated with a lower risk of adverse outcomes. This highlights the potential utility of a data-driven approach in the diagnostic management of CAD., Competing Interests: Conflict of interest: E.K.O. is a co-inventor in patent applications (US17/720,068, 63/619,241, 63/177,117, 63/580,137, 63/606,203, 63/562,335, WO2018078395A1, and WO2020058713A1), has been a consultant for Caristo Diagnostics Ltd and Ensight-AI Inc, and received royalty fees for technology licensed through the University of Oxford related to computed tomography phenotyping of cardiometabolic risk. E.K.O. and R.K. are academic cofounders of Evidence2Health, a health data analytics company. R.K. is an associate editor of JAMA. He receives research support through Yale, from Bristol-Myers Squibb, Novo Nordisk, and BridgeBio. He is a co-inventor of US Provisional Patent Applications 63/177,117, 63/428,569, 63/346,610, 63/484,426, 63/508,315, 63/606,203, 63/619,241, 63/562,335 and co-founder of Ensight-AI, Inc. H.M.K. works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programmes, was a recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the co-founder of Hugo Health, a personal health information platform, and co-founder of Refactor Health, a healthcare AI-augmented data management company, and Ensight-AI, Inc. All other authors declare no relevant competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Current risk stratification strategies for heart failure (HF) risk require either specific blood-based biomarkers or comprehensive clinical evaluation. In this study, we evaluated the use of artificial intelligence (AI) applied to images of electrocardiograms (ECGs) to predict HF risk., Methods: Across multinational longitudinal cohorts in the integrated Yale New Haven Health System (YNHHS) and in population-based UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we identified individuals without HF at baseline. Incident HF was defined based on the first occurrence of an HF hospitalization. We evaluated an AI-ECG model that defines the cross-sectional probability of left ventricular dysfunction from a single image of a 12-lead ECG and its association with incident HF. We accounted for the competing risk of death using the Fine-Gray subdistribution model and evaluated the discrimination using Harrel's c-statistic. The pooled cohort equations to prevent HF (PCP-HF) were used as a comparator for estimating incident HF risk., Results: Among 231,285 individuals at YNHHS, 4472 had a primary HF hospitalization over 4.5 years (IQR 2.5-6.6) of follow-up. In UKB and ELSA-Brasil, among 42,741 and 13,454 people, 46 and 31 developed HF over a follow-up of 3.1 (2.1-4.5) and 4.2 (3.7-4.5) years, respectively. A positive AI-ECG screen portended a 4-fold higher risk of incident HF among YNHHS patients (age-, sex-adjusted HR [aHR] 3.88 [95% CI, 3.63-4.14]). In UKB and ELSA-Brasil, a positive-screen ECG portended 13- and 24-fold higher hazard of incident HF, respectively (aHR: UKBB, 12.85 [6.87-24.02]; ELSA-Brasil, 23.50 [11.09-49.81]). The association was consistent after accounting for comorbidities and the competing risk of death. Higher model output probabilities were progressively associated with a higher risk for HF. The model's discrimination for incident HF was 0.718 in YNHHS, 0.769 in UKB, and 0.810 in ELSA-Brasil. Across cohorts, incorporating model probability with PCP-HF yielded a significant improvement in discrimination over PCP-HF alone., Conclusions: An AI model applied to images of 12-lead ECGs can identify those at elevated risk of HF across multinational cohorts. As a digital biomarker of HF risk that requires just an ECG image, this AI-ECG approach can enable scalable and efficient screening for HF risk.

Introduction: Serial functional status assessments are critical to heart failure (HF) management but are often described narratively in documentation, limiting their use in quality improvement or patient selection for clinical trials. We developed and validated a deep learning-based natural language processing (NLP) strategy to extract functional status assessments from unstructured clinical notes., Methods: We identified 26,577 HF patients across outpatient services at Yale New Haven Hospital (YNHH), Greenwich Hospital (GH), and Northeast Medical Group (NMG) (mean age 76.1 years; 52.0% women). We used expert annotated notes from YNHH for model development/internal testing and from GH and NMG for external validation. The primary outcomes were NLP models to detect (a) explicit New York Heart Association (NYHA) classification, (b) HF symptoms during activity or rest, and (c) functional status assessment frequency., Results: Among 3,000 expert-annotated notes, 13.6% mentioned NYHA class, and 26.5% described HF symptoms. The model to detect NYHA classes achieved a class-weighted AUROC of 0.99 (95% CI: 0.98-1.00) at YNHH, 0.98 (0.96-1.00) at NMG, and 0.98 (0.92-1.00) at GH. The activity-related HF symptom model achieved an AUROC of 0.94 (0.89-0.98) at YNHH, 0.94 (0.91-0.97) at NMG, and 0.95 (0.92-0.99) at GH. Deploying the NYHA model among 166,655 unannotated notes from YNHH identified 21,528 (12.9%) with NYHA mentions and 17,642 encounters (10.5%) classifiable into functional status groups based on activity-related symptoms., Conclusions: We developed and validated an NLP approach to extract NYHA classification and activity-related HF symptoms from clinical notes, enhancing the ability to track optimal care and identify trial-eligible patients.

Background: Risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability., Objectives: To examine an artificial intelligence (AI)-enhanced electrocardiographic (AI-ECG) surrogate for imaging risk biomarkers, and its association with CTRCD., Methods: Across a five-hospital U.S.-based health system (2013-2023), we identified patients with breast cancer or non-Hodgkin lymphoma (NHL) who received anthracyclines (AC) and/or trastuzumab (TZM), and a control cohort receiving immune checkpoint inhibitors (ICI). We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to ECG images (≥0.1, positive screen) and explored its association with i) global longitudinal strain (GLS) measured within 15 days ( n =7,271 pairs); ii) future CTRCD (new cardiomyopathy, heart failure, or left ventricular ejection fraction [LVEF]<50%), and LVEF<40%. In the ICI cohort we correlated baseline AI-ECG-LVSD predictions with downstream myocarditis., Results: Higher AI-ECG LVSD predictions were associated with worse GLS (-18% [IQR:-20 to -17%] for predictions<0.1, to -12% [IQR:-15 to -9%] for ≥0.5 ( p <0.001)). In 1,308 patients receiving AC/TZM (age 59 [IQR:49-67] years, 999 [76.4%] women, 80 [IQR:42-115] follow-up months) a positive baseline AI-ECG LVSD screen was associated with ~2-fold and ~4.8-fold increase in the incidence of the composite CTRCD endpoint (adj.HR 2.22 [95%CI:1.63-3.02]), and LVEF<40% (adj.HR 4.76 [95%CI:2.62-8.66]), respectively. Among 2,056 patients receiving ICI (age 65 [IQR:57-73] years, 913 [44.4%] women, follow-up 63 [IQR:28-99] months) AI-ECG predictions were not associated with ICI myocarditis (adj.HR 1.36 [95%CI:0.47-3.93])., Conclusion: AI applied to baseline ECG images can stratify the risk of CTRCD associated with anthracycline or trastuzumab exposure.

Background: Artificial intelligence-enhanced electrocardiography (AI-ECG) can identify hypertrophic cardiomyopathy (HCM) on 12-lead ECGs and offers a novel way to monitor treatment response. While the surgical or percutaneous reduction of the interventricular septum (SRT) represented initial HCM therapies, mavacamten offers an oral alternative., Objective: To evaluate biological response to SRT and mavacamten., Methods: We applied an AI-ECG model for HCM detection to ECG images from patients who underwent SRT across three sites: Yale New Haven Health System (YNHHS), Cleveland Clinic Foundation (CCF), and Atlantic Health System (AHS); and to ECG images from patients receiving mavacamten at YNHHS., Results: A total of 70 patients underwent SRT at YNHHS, 100 at CCF, and 145 at AHS. At YNHHS, there was no significant change in the AI-ECG HCM score before versus after SRT (pre-SRT: median 0.55 [IQR 0.24-0.77] vs post-SRT: 0.59 [0.40-0.75]). The AI-ECG HCM scores also did not improve post SRT at CCF (0.61 [0.32-0.79] vs 0.69 [0.52-0.79]) and AHS (0.52 [0.35-0.69] vs 0.61 [0.49-0.70]). Among 36 YNHHS patients on mavacamten therapy, the median AI-ECG score before starting mavacamten was 0.41 (0.22-0.77), which decreased significantly to 0.28 (0.11-0.50, p <0.001 by Wilcoxon signed-rank test) at the end of a median follow-up period of 237 days., Conclusions: The lack of improvement in AI-based HCM score with SRT, in contrast to a significant decrease with mavacamten, suggests the potential role of AI-ECG for serial monitoring of pathophysiological improvement in HCM at the point-of-care using ECG images.

Timely and accurate assessment of electrocardiograms (ECGs) is crucial for diagnosing, triaging, and clinically managing patients. Current workflows rely on a computerized ECG interpretation using rule-based tools built into the ECG signal acquisition systems with limited accuracy and flexibility. In low-resource settings, specialists must review every single ECG for such decisions, as these computerized interpretations are not available. Additionally, high-quality interpretations are even more essential in such low-resource settings as there is a higher burden of accuracy for automated reads when access to experts is limited. Artificial Intelligence (AI)-based systems have the prospect of greater accuracy yet are frequently limited to a narrow range of conditions and do not replicate the full diagnostic range. Moreover, these models often require raw signal data, which are unavailable to physicians and necessitate costly technical integrations that are currently limited. To overcome these challenges, we developed and validated a format-independent vision encoder-decoder model - ECG-GPT - that can generate free-text, expert-level diagnosis statements directly from ECG images. The model shows robust performance, validated on 2.6 million ECGs across 6 geographically distinct health settings: (1) 2 large and diverse US health systems- Yale-New Haven and Mount Sinai Health Systems, (2) a consecutive ECG dataset from a central ECG repository from Minas Gerais, Brazil, (3) the prospective cohort study, UK Biobank, (4) a Germany-based, publicly available repository, PTB-XL, and (5) a community hospital in Missouri. The model demonstrated consistently high performance (AUROC≥0.81) across a wide range of rhythm and conduction disorders. This can be easily accessed via a web-based application capable of receiving ECG images and represents a scalable and accessible strategy for generating accurate, expert-level reports from images of ECGs, enabling accurate triage of patients globally, especially in low-resource settings., Competing Interests: Competing Interests: Mr. Khunte, Mr. Sangha, and Dr. Khera are the coinventors of U.S. Provisional Patent Application No. 63/428,569. Mr. Sangha and Dr. Khera are the coinventors of U.S. Pending Patent Application No. 63/346,610, and are co-founders of Ensight-AI with Dr. Krumholz. Dr. Khera is the coinventor of U.S. Provisional Patent Application No. 63/177,117 (unrelated to current work) and is a co-founder of Evidence2Health, a precision health platform for evidence-based care. He is also an associate editor at JAMA, and received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award, 2022060). He also receives research support, through Yale, from Bristol-Myers Squibb, Novo Nordisk, and BridgeBio. Dr. Oikonomou receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award 1F32HL170592). He is an academic co-founder of Evidence2Health LLC, a co-inventor in patent applications (US17/720,068, 63/177,117, 63/580,137, 63/606,203, WO2018078395A1, WO2020058713A1) and has been an ad hoc consultant for Caristo Diagnostics Ltd. Dr. Nadkarni is a founder of Renalytix, Pensieve, and Verici and provides consultancy services to AstraZeneca, Reata, Renalytix, Siemens Healthineer, and Variant Bio, and serves a scientific advisory board member for Renalytix and Pensieve. He also has equity in Renalytix, Pensieve, and Verici. Dr. Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs, was a recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the co-founder of Hugo Health, a personal health information platform, and co-founder of Refactor Health, a healthcare AI-augmented data management company, and Ensight-AI, Inc. All other authors declare no relevant competing interests. Dr. Bhatt discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo.

Background: SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials., Methods: Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis., Findings: Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13])., Interpretation: In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD., Funding: National Institutes of Health, United States Department of Veterans Affairs.

Background: Hypertrophic cardiomyopathy (HCM) affects 1 in every 200 individuals and is the leading cause of sudden cardiac death in young adults. HCM can be identified using an electrocardiogram (ECG) raw voltage data and deep learning approaches, but their point-of-care application is limited by the inaccessibility of these signal data. We developed a deep learning-based approach that overcomes this limitation and detects HCM from images of 12-lead ECGs across layouts., Methods: We identified ECGs from patients with HCM features present on cardiac magnetic resonance imaging (CMR) or those within 30 days of an echocardiogram documenting thickened interventricular septum (end-diastolic interventricular septum thickness > 15mm). Patients with CMR-confirmed HCM were considered as cases during the final model evaluation. The model was validated within clinical settings at YNHH and externally on ECG images from the prospective, population-based UK Biobank cohort. We localized class-discriminating signals in ECG images using gradient-weighted class activation mapping., Results: Overall, 124,553 ECGs from 66,987 individuals (HCM cases and controls) were used for model development. The model demonstrated high discrimination for HCM across various ECG image formats and calibrations in internal validation (area under receiving operation characteristics [AUROC] 0.96) and external sets of ECG images from UK Biobank (AUROC 0.94). A positive screen for HCM was associated with a 100-fold higher odds of CMR-confirmed HCM (OR 102.4, 95% Confidence Interval, 57.4 - 182.6) in the held-out set. Class-discriminative patterns localized to the anterior and lateral leads (V4-V5)., Conclusions: We developed and externally validated a deep learning model that identifies HCM from ECG images with excellent discrimination. This approach represents an automated, efficient, and accessible screening strategy for HCM., Competing Interests: Mr. Sangha and Dr. Khera are the coinventors of U.S. Provisional Patent Application No. 63/346,610, “Articles and methods for format-independent detection of hidden cardiovascular disease from printed electrocardiographic images using deep learning” and are co-founders of Ensight-AI. Dr. Khera receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060). He receives support from the Blavatnik Foundation through the Blavatnik fund for Innovation at Yale. He also receives research support, through Yale, from Bristol-Myers Squibb, and Novo Nordisk. He is an Associate Editor at JAMA. In addition to 63/346,610, Dr. Khera is a coinventor of U.S. Provisional Patent Applications 63/177,117, 63/428,569, and 63/484,426. Dr. Khera and Dr. Oikonomou are co-founders of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. Dr. Oikonomou is a co-inventor of the U.S. Patent Applications 63/508,315 & 63/177,117 and has served as a consultant to Caristo Diagnostics Ltd (all outside the current work).

Importance: Despite efforts to improve the quality of care for patients with atherosclerotic cardiovascular disease (ASCVD), it is unclear whether the US has made progress in reducing racial and ethnic differences in utilization of guideline-recommended therapies for secondary prevention., Objective: To evaluate 21-year trends in racial and ethnic differences in utilization of guideline-recommended pharmacological medications and lifestyle modifications among US adults with ASCVD., Design, Setting, and Participants: This cross-sectional study includes data from the National Health and Nutrition Examination Survey between 1999 and 2020. Eligible participants were adults aged 18 years or older with a history of ASCVD. Data were analyzed between March 2022 and May 2023., Exposure: Self-reported race and ethnicity., Main Outcome and Measures: Rates and racial and ethnic differences in the use of guideline-recommended pharmacological medications and lifestyle modifications., Results: The study included 5218 adults with a history of ASCVD (mean [SD] age, 65.5 [13.2] years, 2148 women [weighted average, 44.2%]), among whom 1170 (11.6%) were Black, 930 (7.7%) were Hispanic or Latino, and 3118 (80.7%) were White in the weighted sample. Between 1999 and 2020, there was a significant increase in total cholesterol control and statin use in all racial and ethnic subgroups, and in angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) utilization in non-Hispanic White individuals and Hispanic and Latino individuals (Hispanic and Latino individuals: 17.12 percentage points; 95% CI, 0.37-37.88 percentage points; P = .046; non-Hispanic White individuals: 12.14 percentage points; 95% CI, 6.08-18.20 percentage points; P < .001), as well as smoking cessation within the Hispanic and Latino population (-27.13 percentage points; 95% CI, -43.14 to -11.12 percentage points; P = .002). During the same period, the difference in smoking cessation between Hispanic and Latino individuals and White individuals was reduced (-24.85 percentage points; 95% CI, -38.19 to -11.51 percentage points; P < .001), but racial and ethnic differences for other metrics did not change significantly. Notably, substantial gaps persisted between current care and optimal care throughout the 2 decades of data analyzed. In the period of 2017 to 2020, optimal regimens were observed in 47.4% (95% CI, 39.3%-55.4%), 48.7% (95% CI, 36.7%-60.6%), and 53.0% (95% CI, 45.6%-60.4%) of Black, Hispanic and Latino, and White individuals, respectively., Conclusions and Relevance: In this cross-sectional study of US adults with ASCVD, significant disparities persisted between current care and optimal care, surpassing any differences observed among demographic groups. These findings highlight the critical need for sustained efforts to bridge these gaps and achieve better outcomes for all patients, regardless of their racial and ethnic backgrounds.

Objective: To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin., Design: Federated pharmacoepidemiological evaluation in LEGEND-T2DM., Setting: 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021., Participants: 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments., Exposure: The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort., Main Outcomes Measures: The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated., Results: 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease., Conclusions: Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus., Competing Interests: Competing interests: This study is undertaken within Observational Health Data Sciences and Informatics, an open collaboration. RK received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award, 2022060). He is an Associate Editor of JAMA. He also receives research support, through Yale, from Bristol-Myers Squibb. He is a coinventor of US Provisional Patent Applications 63/177,117 and 63/346,610, unrelated to current work. He is also a founder of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. TD-S acknowledges receiving financial support from the Instituto de Salud Carlos III (ISCIII; Miguel Servet 2021: CP21/00023). KKCM reports grants from C W Maplethorpe Fellowship, grants from National Institute of Health Research, UK, grants from European Commission Framwork Horizon 2020, grants from Hong Kong Research Grant Council, grants from Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and personal fees from IQVIA outside of the submitted work. DRM was supported by a Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). MJS is an employee and shareholder of Johnson & Johnson. HK received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm. He is a co-founder of Refactor Health and HugoHealth, and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare and Medicaid Services and through Yale University from Johnson & Johnson. MAS receives contracts and grants from the National Institutes of Health, the US Department of Veterans Affairs, the US Food and Drug Administration and Janssen Research and Development, the latter two of which are outside the scope of this work. Other authors declare no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD) and major adverse cardiovascular events (MACE). However, fewer than 0.5% of patients undergo Lp(a) testing, limiting the evaluation and use of novel targeted therapeutics currently under development., Objective: We developed and validated a machine learning model to enable targeted screening for elevated Lp(a)., Design: Cross-sectional., Setting: 4 multinational population-based cohorts., Participants: We included 456,815 participants from the UK Biobank (UKB), the largest cohort with protocolized Lp(a) testing for model development. The model's external validity was assessed in Atherosclerosis Risk in Communities (ARIC) (N=14,484), Coronary Artery Risk Development in Young Adults (CARDIA) (N=4,124), and Multi-Ethnic Study of Atherosclerosis (MESA) (N=4,672) cohorts., Exposures: Demographics, medications, diagnoses, procedures, vitals, and laboratory measurements from UKB and linked electronic health records (EHR) were candidate input features to predict high Lp(a). We used the pooled cohort equations (PCE), an ASCVD risk marker, as a comparator to identify elevated Lp(a)., Main Outcomes and Measures: The main outcome was elevated Lp(a) (≥150 nmol/L), and the number-needed-to-test (NNT) to find one case with elevated Lp(a). We explored the association of the model's prediction probabilities with all-cause and cardiovascular mortality, and MACE., Results: The Algorithmic Risk Inspection for Screening Elevated Lp(a) (ARISE) used low-density lipoprotein cholesterol, statin use, triglycerides, high-density lipoprotein cholesterol, history of ASCVD, and anti-hypertensive medication use as input features. ARISE outperformed cardiovascular risk stratification through PCE for predicting elevated Lp(a) with a significantly lower NNT (4.0 versus 8.0 [with or without PCE], P<0.001). ARISE performed comparably across external validation cohorts and subgroups, reducing the NNT by up to 67.3%, depending on the probability threshold. Over a median follow-up of 4.2 years, a high ARISE probability was also associated with a greater hazard of all-cause death and MACE (age/sex-adjusted hazard ratio [aHR], 1.35, and 1.38, respectively, P<0.001), with a greater increase in cardiovascular mortality (aHR, 2.17, P<0.001)., Conclusions and Relevance: ARISE optimizes screening for elevated Lp(a) using commonly available clinical features. ARISE can be deployed in EHR and other settings to encourage greater Lp(a) testing and to improve identifying cases eligible for novel targeted therapeutics in trials., Key Points: Question: How can we optimize the identification of individuals with elevated lipoprotein(a) [Lp(a)] who may be eligible for novel targeted therapeutics? Findings: Using 4 multinational population-based cohorts, we developed and validated a machine learning model, Algorithmic Risk Inspection for Screening Elevated Lp(a) (ARISE), to enable targeted screening for elevated Lp(a). In contrast to the pooled cohort equations that do not identify those with elevated Lp(a), ARISE reduces the "number-needed-to-test" to find one case with elevated Lp(a) by up to 67.3%. Meaning: ARISE can be deployed in electronic health records and other settings to enable greater yield of Lp(a) testing, thereby improving the identification of individuals with elevated Lp(a).

The electronic health record (EHR) represents a rich source of patient information, increasingly being leveraged for cardiovascular research. Although its primary use remains the seamless delivery of health care, the various longitudinally aggregated structured and unstructured data elements for each patient within the EHR can define the computational phenotypes of disease and care signatures and their association with outcomes. Although structured data elements, such as demographic characteristics, laboratory measurements, problem lists, and medications, are easily extracted, unstructured data are underused. The latter include free text in clinical narratives, documentation of procedures, and reports of imaging and pathology. Rapid scaling up of data storage and rapid innovation in natural language processing and computer vision can power insights from unstructured data streams. However, despite an array of opportunities for research using the EHR, specific expertise is necessary to adequately address confidentiality, accuracy, completeness, and heterogeneity challenges in EHR-based research. These often require methodological innovation and best practices to design and conduct successful research studies. Our review discusses these challenges and their proposed solutions. In addition, we highlight the ongoing innovations in federated learning in the EHR through a greater focus on common data models and discuss ongoing work that defines such an approach to large-scale, multicenter, federated studies. Such parallel improvements in technology and research methods enable innovative care and optimization of patient outcomes., Competing Interests: Declaration of Competing Interest Dr. Khera is an Associate Editor of JAMA. He receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award number K23HL153775) and the Doris Duke Charitable Foundation (under award number 2022060). He also receives research support, through Yale, from Bristol-Myers Squibb and Novo Nordisk. He is a coinventor of US Provisional patent applications 63/177,117, 63/428,569, 63/346,610, and 63/484,426. He is a cofounder of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.

Background: Smartphone-based health applications are increasingly popular, but their real-world use for cardiovascular risk management remains poorly understood., Objectives: The purpose of this study was to investigate the patterns of tracking health goals using smart devices, including smartphones and/or tablets, in the United States., Methods: Using the nationally representative Health Information National Trends Survey for 2017 to 2020, we examined self-reported tracking of health-related goals (optimizing body weight, increasing physical activity, and/or quitting smoking) using smart devices among those with cardiovascular disease (CVD) or cardiovascular risk factors of hypertension, diabetes, obesity, and/or smoking. Survey analyses were used to obtain national estimates of use patterns and identify features associated with the use of these devices for tracking health goals., Results: Of 16,092 Health Information National Trends Survey participants, 10,660 had CVD or cardiovascular risk factors, representing 154.2 million (95% CI: 149.2-159.3 million) U.S. adults. Among the general U.S. adult population, 46% (95% CI: 44%-47%) tracked their health goals using their smart devices, compared with 42% (95% CI: 40%-43%) of those with or at risk of CVD. Younger age, female, Black race, higher educational attainment, and greater income were independently associated with tracking of health goals using smart devices., Conclusions: Two in 5 U.S. adults with or at risk of CVD use their smart devices to track health goals. While representing a potential avenue to improve care, the lower use of smart devices among older and low-income individuals, who are at higher risk of adverse cardiovascular outcomes, requires that digital health interventions are designed so as not to exacerbate existing disparities.

Background: Left ventricular (LV) systolic dysfunction is associated with a >8-fold increased risk of heart failure and a 2-fold risk of premature death. The use of ECG signals in screening for LV systolic dysfunction is limited by their availability to clinicians. We developed a novel deep learning-based approach that can use ECG images for the screening of LV systolic dysfunction., Methods: Using 12-lead ECGs plotted in multiple different formats, and corresponding echocardiographic data recorded within 15 days from the Yale New Haven Hospital between 2015 and 2021, we developed a convolutional neural network algorithm to detect an LV ejection fraction <40%. The model was validated within clinical settings at Yale New Haven Hospital and externally on ECG images from Cedars Sinai Medical Center in Los Angeles, CA; Lake Regional Hospital in Osage Beach, MO; Memorial Hermann Southeast Hospital in Houston, TX; and Methodist Cardiology Clinic of San Antonio, TX. In addition, it was validated in the prospective Brazilian Longitudinal Study of Adult Health. Gradient-weighted class activation mapping was used to localize class-discriminating signals on ECG images., Results: Overall, 385 601 ECGs with paired echocardiograms were used for model development. The model demonstrated high discrimination across various ECG image formats and calibrations in internal validation (area under receiving operation characteristics [AUROCs], 0.91; area under precision-recall curve [AUPRC], 0.55); and external sets of ECG images from Cedars Sinai (AUROC, 0.90 and AUPRC, 0.53), outpatient Yale New Haven Hospital clinics (AUROC, 0.94 and AUPRC, 0.77), Lake Regional Hospital (AUROC, 0.90 and AUPRC, 0.88), Memorial Hermann Southeast Hospital (AUROC, 0.91 and AUPRC 0.88), Methodist Cardiology Clinic (AUROC, 0.90 and AUPRC, 0.74), and Brazilian Longitudinal Study of Adult Health cohort (AUROC, 0.95 and AUPRC, 0.45). An ECG suggestive of LV systolic dysfunction portended >27-fold higher odds of LV systolic dysfunction on transthoracic echocardiogram (odds ratio, 27.5 [95% CI, 22.3-33.9] in the held-out set). Class-discriminative patterns localized to the anterior and anteroseptal leads (V 2 and V 3 ), corresponding to the left ventricle regardless of the ECG layout. A positive ECG screen in individuals with an LV ejection fraction ≥40% at the time of initial assessment was associated with a 3.9-fold increased risk of developing incident LV systolic dysfunction in the future (hazard ratio, 3.9 [95% CI, 3.3-4.7]; median follow-up, 3.2 years)., Conclusions: We developed and externally validated a deep learning model that identifies LV systolic dysfunction from ECG images. This approach represents an automated and accessible screening strategy for LV systolic dysfunction, particularly in low-resource settings., Competing Interests: Disclosures Dr Mortazavi reported receiving grants from the National Institute of Biomedical Imaging and Bioengineering, National Heart, Lung, and Blood Institute, US Food and Drug Administration, and the US Department of Defense Advanced Research Projects Agency outside the submitted work; in addition, Dr Mortazavi has a pending patent on predictive models using electronic health records (US20180315507A1). Dr A.H. Ribeiro is funded by the Kjell och Märta Beijer Foundation. Dr Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs, was a recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a cardiac scientific advisory board for UnitedHealth; was a member of the IBM Watson Health Life Sciences board; is a member of the advisory board for element science, the advisory board for Facebook, and the physician advisory board for Aetna; and is co-founder of Hugo Health, a personal health information platform, and co-founder of Refactor Health, a health care artificial intelligence–augmented data management company. Dr A.L.P. Ribeiro is supported in part by CNPq (465518/2014-1, 310790/2021-2, and 409604/2022-4) and by FAPEMIG (PPM-00428-17, RED-00081-16, and PPE-00030-21). V. Sangha and Dr Khera are the coinventors of US provisional patent application No. 63/346,610, “Articles and methods for format-independent detection of hidden cardiovascular disease from printed electrocardiographic images using deep learning.” Dr Khera receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060). He receives support from the Blavatnik Foundation through the Blavatnik fund for innovation at Yale. He also receives research support, through Yale, from Bristol-Myers Squibb, and Novo Nordisk. He is an associate editor for JAMA. In addition to 63/346,610, Dr Khera is a coinventor of US provisional patent applications 63/177,117, 63/428,569, and 63/484,426. He is also a founder of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care.

Artificial intelligence (AI) can detect left ventricular systolic dysfunction (LVSD) from electrocardiograms (ECGs). Wearable devices could allow for broad AI-based screening but frequently obtain noisy ECGs. We report a novel strategy that automates the detection of hidden cardiovascular diseases, such as LVSD, adapted for noisy single-lead ECGs obtained on wearable and portable devices. We use 385,601 ECGs for development of a standard and noise-adapted model. For the noise-adapted model, ECGs are augmented during training with random gaussian noise within four distinct frequency ranges, each emulating real-world noise sources. Both models perform comparably on standard ECGs with an AUROC of 0.90. The noise-adapted model performs significantly better on the same test set augmented with four distinct real-world noise recordings at multiple signal-to-noise ratios (SNRs), including noise isolated from a portable device ECG. The standard and noise-adapted models have an AUROC of 0.72 and 0.87, respectively, when evaluated on ECGs augmented with portable ECG device noise at an SNR of 0.5. This approach represents a novel strategy for the development of wearable-adapted tools from clinical ECG repositories., (© 2023. The Author(s).)

Importance: Wearable devices may be able to improve cardiovascular health, but the current adoption of these devices could be skewed in ways that could exacerbate disparities., Objective: To assess sociodemographic patterns of use of wearable devices among adults with or at risk for cardiovascular disease (CVD) in the US population in 2019 to 2020., Design, Setting, and Participants: This population-based cross-sectional study included a nationally representative sample of the US adults from the Health Information National Trends Survey (HINTS). Data were analyzed from June 1 to November 15, 2022., Exposures: Self-reported CVD (history of heart attack, angina, or congestive heart failure) and CVD risk factors (≥1 risk factor among hypertension, diabetes, obesity, or cigarette smoking)., Main Outcomes and Measures: Self-reported access to wearable devices, frequency of use, and willingness to share health data with clinicians (referred to as health care providers in the survey)., Results: Of the overall 9303 HINTS participants representing 247.3 million US adults (mean [SD] age, 48.8 [17.9] years; 51% [95% CI, 49%-53%] women), 933 (10.0%) representing 20.3 million US adults had CVD (mean [SD] age, 62.2 [17.0] years; 43% [95% CI, 37%-49%] women), and 5185 (55.7%) representing 134.9 million US adults were at risk for CVD (mean [SD] age, 51.4 [16.9] years; 43% [95% CI, 37%-49%] women). In nationally weighted assessments, an estimated 3.6 million US adults with CVD (18% [95% CI, 14%-23%]) and 34.5 million at risk for CVD (26% [95% CI, 24%-28%]) used wearable devices compared with an estimated 29% (95% CI, 27%-30%) of the overall US adult population. After accounting for differences in demographic characteristics, cardiovascular risk factor profile, and socioeconomic features, older age (odds ratio [OR], 0.35 [95% CI, 0.26-0.48]), lower educational attainment (OR, 0.35 [95% CI, 0.24-0.52]), and lower household income (OR, 0.42 [95% CI, 0.29-0.60]) were independently associated with lower use of wearable devices in US adults at risk for CVD. Among wearable device users, a smaller proportion of adults with CVD reported using wearable devices every day (38% [95% CI, 26%-50%]) compared with overall (49% [95% CI, 45%-53%]) and at-risk (48% [95% CI, 43%-53%]) populations. Among wearable device users, an estimated 83% (95% CI, 70%-92%) of US adults with CVD and 81% (95% CI, 76%-85%) at risk for CVD favored sharing wearable device data with their clinicians to improve care., Conclusions and Relevance: Among individuals with or at risk for CVD, fewer than 1 in 4 use wearable devices, with only half of those reporting consistent daily use. As wearable devices emerge as tools that can improve cardiovascular health, the current use patterns could exacerbate disparities unless there are strategies to ensure equitable adoption.

Objective: Nonexercise algorithms are cost-effective methods to estimate cardiorespiratory fitness (CRF), but the existing models have limitations in generalizability and predictive power. This study aims to improve the nonexercise algorithms using machine learning (ML) methods and data from US national population surveys., Materials and Methods: We used the 1999-2004 data from the National Health and Nutrition Examination Survey (NHANES). Maximal oxygen uptake (VO2 max), measured through a submaximal exercise test, served as the gold standard measure for CRF in this study. We applied multiple ML algorithms to build 2 models: a parsimonious model using commonly available interview and examination data, and an extended model additionally incorporating variables from Dual-Energy X-ray Absorptiometry (DEXA) and standard laboratory tests in clinical practice. Key predictors were identified using Shapley additive explanation (SHAP)., Results: Among the 5668 NHANES participants in the study population, 49.9% were women and the mean (SD) age was 32.5 years (10.0). The light gradient boosting machine (LightGBM) had the best performance across multiple types of supervised ML algorithms. Compared with the best existing nonexercise algorithms that could be applied to the NHANES, the parsimonious LightGBM model (RMSE: 8.51 ml/kg/min [95% CI: 7.73-9.33]) and the extended LightGBM model (RMSE: 8.26 ml/kg/min [95% CI: 7.44-9.09]) significantly reduced the error by 15% and 12% (P < .001 for both), respectively., Discussion: The integration of ML and national data source presents a novel approach for estimating cardiovascular fitness. This method provides valuable insights for cardiovascular disease risk classification and clinical decision-making, ultimately leading to improved health outcomes., Conclusion: Our nonexercise models provide improved accuracy in estimating VO2 max within NHANES data as compared to existing nonexercise algorithms., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Antimicrobial resistance (AMR) is the next big pandemic that threatens humanity. The One Health approach to AMR requires quantification of interactions between health, demographic, socioeconomic, environmental, and geopolitical factors to design interventions. This study is focused on learning health system factors on global AMR., Methods: This study analysed longitudinal data (2004-2017) of AMR having 6 33 820 isolates from 70 middle and high-income countries. We integrated AMR data with the Global Burden of Disease (GBD), Governance (WGI), and Finance data sets to find AMR's unbiased and actionable determinants. We chose a Bayesian decision network (BDN) approach within the causal modelling framework to quantify determinants of AMR. Further, we integrated Bayesian networks' global knowledge discovery approach with discriminative machine learning to predict individual-level antibiotic susceptibility in patients., Results: From MAR (multiple antibiotic resistance) scores, we found a non-uniform spread pattern of AMR. Components-level analysis revealed that governance, finance, and disease burden variables strongly correlate with AMR. From the Bayesian network analysis, we found that access to immunization, obstetric care, and government effectiveness are strong, actionable factors in reducing AMR, confirmed by what-if analysis. Finally, our discriminative machine learning models achieved an individual-level AUROC (Area under receiver operating characteristic curve) of 0.94 (SE = 0.01) and 0.89 (SE = 0.002) to predict Staphylococcus aureus resistance to ceftaroline and oxacillin, respectively., Conclusion: Causal machine learning revealed that immunisation strategies and quality of governance are vital, actionable interventions to reduce AMR., (Copyright © 2022. Published by Elsevier Ltd.)

The COVID-19 pandemic has revealed the power of internet disinformation in influencing global health. The deluge of information travels faster than the epidemic itself and is a threat to the health of millions across the globe. Health apps need to leverage machine learning for delivering the right information while constantly learning misinformation trends and deliver these effectively in vernacular languages in order to combat the infodemic at the grassroot levels in the general public. Our application, WashKaro, is a multi-pronged intervention that uses conversational Artificial Intelligence (AI), machine translation, and natural language processing to combat misinformation (NLP). WashKaro uses AI to provide accurate information matched against WHO recommendations and delivered in an understandable format in local languages. The primary aim of this study was to assess the use of neural models for text summarization and machine learning for delivering WHO matched COVID-19 information to mitigate the misinfodemic. The secondary aim of this study was to develop a symptom assessment tool and segmentation insights for improving the delivery of information. A total of 5026 people downloaded the app during the study window; among those, 1545 were actively engaged users. Our study shows that 3.4 times more females engaged with the App in Hindi as compared to males, the relevance of AI-filtered news content doubled within 45 days of continuous machine learning, and the prudence of integrated AI chatbot "Satya" increased thus proving the usefulness of a mHealth platform to mitigate health misinformation. We conclude that a machine learning application delivering bite-sized vernacular audios and conversational AI is a practical approach to mitigate health misinformation., (© 2022. The Author(s).)

Poor hypertension awareness and underuse of guideline-recommended medications are critical factors contributing to poor hypertension control. Using data from 8095 hypertensive people aged ≥18 years from the National Health and Nutrition Examination Survey (2011-2018), we examined recent trends in racial and ethnic differences in awareness and antihypertensive medication use, and their association with racial and ethnic differences in hypertension control. Between 2011 and 2018, age-adjusted hypertension awareness declined for Black, Hispanic, and White individuals, but the 3 outcomes increased or did not change for Asian individuals. Compared with White individuals, Black individuals had a similar awareness (odds ratio, 1.20 [0.96-1.45]) and overall treatment rates (1.04 [0.84-1.25]), and received more intensive antihypertensive medication if treated (1.41 [1.27-1.56]), but had a lower control rate (0.72 [0.61-0.83]). Asian and Hispanic individuals had significantly lower awareness rates (0.69 [0.52-0.85] and 0.74 [0.59-0.89]), overall treatment rates (0.72 [0.57-0.88] and 0.69 [0.55-0.82]), received less intensive medication if treated (0.60 [0.50-0.72] and 0.86 [0.75-0.96]), and had lower control rates (0.66 [0.54-0.79] and 0.69 [0.57-0.81]). The racial and ethnic differences in awareness, treatment, and control persisted over the study period and were consistent across age, sex, and income strata. Lower awareness and treatment were significantly associated with lower control in Asian and Hispanic individuals ( P <0.01 for all) but not in Black individuals. These findings highlight the need for interventions to improve awareness and treatment among Asian and Hispanic individuals, and more investigation into the downstream factors that may contribute to the poor hypertension control among Black individuals.

Background: Teleneurology consultations can be highly advantageous since neurological diseases and disabilities often limit patient's access to health care, particularly in a setting where they need to travel long distances for specialty consults. Patient satisfaction is an important outcome assessing success of a telemedicine program. Materials and Methods: A cross-sectional study was conducted to determine satisfaction and perception of patients toward an audio call based teleneurology follow-up initiated during the coronavirus disease 2019 pandemic. Primary outcomes were satisfaction to tele-consult, and proportion of patients preferring telemedicine for future follow-up. Results: A total of 261 patients who received tele-consult were enrolled. Satisfaction was highest for domain technological quality, followed by patient-physician dialogue (PPD) and least to quality of care (QoC). Median (interquartile range) patient satisfaction on a 5-point Likert scale was 4 (3-5). Eighty-five (32.6%; 95% confidence interval 26.9-38.6%) patients preferred telemedicine for future follow-up. Higher overall satisfaction was associated with health condition being stable/better, change in treatment advised on tele-consult, diagnosis not requiring follow-up examination, higher scores on domains QoC and PPD ( p  < 0.05). Future preference for telemedicine was associated with patient him-/herself consulting with doctor, less duration of follow-up, higher overall satisfaction, and higher scores on domain QoC ( p  < 0.05). On thematic analysis, telemedicine was found convenient, reduced expenditure, and had better physician attention; in-person visits were comprehensive, had better patient-physician relationship, and better communication. Discussion: Patient satisfaction was lower in our study than what has been observed earlier, which may be explained by the primitive nature of our platform. Several variables related to the patients' disease process have an effect on patient satisfaction. Conclusion: Development of robust, structured platforms is necessary to fully utilize the potential of telemedicine in developing countries., Competing Interests: No competing financial interests exist., (© Mudit Agarwal et al., 2021; Published by Mary Ann Liebert, Inc.)

Proactive detection of hemodynamic shock can prevent organ failure and save lives. Thermal imaging is a non-invasive, non-contact modality to capture body surface temperature with the potential to reveal underlying perfusion disturbance in shock. In this study, we automate early detection and prediction of shock using machine learning upon thermal images obtained in a pediatric intensive care unit of a tertiary care hospital. 539 images were recorded out of which 253 had concomitant measurement of continuous intra-arterial blood pressure, the gold standard for shock monitoring. Histogram of oriented gradient features were used for machine learning based region-of-interest segmentation that achieved 96% agreement with a human expert. The segmented center-to-periphery difference along with pulse rate was used in longitudinal prediction of shock at 0, 3, 6 and 12 hours using a generalized linear mixed-effects model. The model achieved a mean area under the receiver operating characteristic curve of 75% at 0 hours (classification), 77% at 3 hours (prediction) and 69% at 12 hours (prediction) respectively. Since hemodynamic shock associated with critical illness and infectious epidemics such as Dengue is often fatal, our model demonstrates an affordable, non-invasive, non-contact and tele-diagnostic decision support system for its reliable detection and prediction.