Performance of contemporary cardiovascular risk stratification scores in Brazil: an evaluation in the ELSA-Brasil study.

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.

Using Artificial Intelligence to Predict Heart Failure Risk from Single-lead Electrocardiographic Signals: A Multinational Assessment.

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 the pooled cohort equations to prevent HF (PCP-HF) score for new-onset HF using Harrel's C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results: There were 194,340 YNHHS patients (age 56 years [IQR, 41-69], 112,082 women [58%]), 42,741 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 3,929 developed HF in YNHHS over 4.5 years (2.6-6.6), 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 resulted in improved Harrel's C-statistic (Δ=0.112-0.114), with an IDI of 0.078-0.238 and an NRI of 20.1%-48.8% for AI-ECG vs. PCP-HF. Conclusions and Relevance: Across multinational cohorts, a noise-adapted AI model with lead I ECGs as the sole input defined HF risk, representing a scalable portable and wearable device-based HF risk-stratification strategy.

Real-world evaluation of an algorithmic machine-learning-guided testing approach in stable chest pain: a multinational, multicohort study.

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 ratioadjusted: 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.

Computational Phenomapping of Randomized Clinical Trials to Enable Assessment of their Real-world Representativeness and Personalized Inference.

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.

A Deep Learning Approach for Automated Extraction of Functional Status and New York Heart Association Class for Heart Failure Patients During Clinical Encounters.

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.

Scalable Risk Stratification for Heart Failure Using Artificial Intelligence applied to 12-lead Electrocardiographic Images: A Multinational Study.

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.

Artificial intelligence-enhanced risk stratification of cancer therapeutics-related cardiac dysfunction using electrocardiographic images.

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.

Study Protocol for the Artificial Intelligence-Driven Evaluation of Structural Heart Diseases Using Wearable Electrocardiogram (ID-SHD).

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).

Automated Diagnostic Reports from Images of Electrocardiograms at the Point-of-Care.

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.

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study.

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.

A Multicenter Evaluation of the Impact of Therapies on Deep Learning-based Electrocardiographic Hypertrophic Cardiomyopathy Markers.

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.

Use of Smart Devices to Track Cardiovascular Health Goals in the United States.

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.

National Trends in Racial and Ethnic Disparities in Use of Recommended Therapies in Adults with Atherosclerotic Cardiovascular Disease, 1999-2020.

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.

Development and Multinational Validation of a Novel Algorithmic Strategy for High Lp(a) Screening.

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).

Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM.

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.

Automated Identification of Heart Failure with Reduced Ejection Fraction using Deep Learning-based Natural Language Processing.

Background: The lack of automated tools for measuring care quality has limited the implementation of a national program to assess and improve guideline-directed care in heart failure with reduced ejection fraction (HFrEF). A key challenge for constructing such a tool has been an accurate, accessible approach for identifying patients with HFrEF at hospital discharge, an opportunity to evaluate and improve the quality of care. Methods: We developed a novel deep learning-based language model for identifying patients with HFrEF from discharge summaries using a semi-supervised learning framework. For this purpose, hospitalizations with heart failure at Yale New Haven Hospital (YNHH) between 2015 to 2019 were labeled as HFrEF if the left ventricular ejection fraction was under 40% on antecedent echocardiography. The model was internally validated with model-based net reclassification improvement (NRI) assessed against chart-based diagnosis codes. We externally validated the model on discharge summaries from hospitalizations with heart failure at Northwestern Medicine, community hospitals of Yale New Haven Health in Connecticut and Rhode Island, and the publicly accessible MIMIC-III database, confirmed with chart abstraction. Results: A total of 13,251 notes from 5,392 unique individuals (mean age 73 ± 14 years, 48% female), including 2,487 patients with HFrEF (46.1%), were used for model development (train/held-out test: 70/30%). The deep learning model achieved an area under receiving operating characteristic (AUROC) of 0.97 and an area under precision-recall curve (AUPRC) of 0.97 in detecting HFrEF on the held-out set. In external validation, the model had high performance in identifying HFrEF from discharge summaries 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 at MIMIC-III. Model-based prediction of HFrEF corresponded to an overall NRI of 60.2 ± 1.9% compared with the chart diagnosis codes (p-value < 0.001) and an increase in AUROC from 0.61 [95% CI: 060-0.63] to 0.91 [95% CI 0.90-0.92]. Conclusions: We developed and externally validated a deep learning language model that automatically identifies HFrEF from clinical notes with high precision and accuracy, representing a key element in automating quality assessment and improvement for individuals with HFrEF.

Detection of left ventricular systolic dysfunction from single-lead electrocardiography adapted for portable and wearable devices.

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.

Detection of Left Ventricular Systolic Dysfunction From Electrocardiographic Images.

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 (V2 and V3), 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.

Cardiovascular Care Innovation through Data-Driven Discoveries in the Electronic Health Record.

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.

Use of Wearable Devices in Individuals With or at Risk for Cardiovascular Disease in the US, 2019 to 2020.

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.