Abstract Background Coronary microvascular dysfunction (CMD) is associated with an increased risk of cardiovascular morbidity and mortality. The current gold-standard comprehensive assessment of CMD is through a limited-access invasive catheterization lab procedure. Purposes We aimed to develop a point-of-care tool to assist clinical guidance in patients presenting with chest pain and/or an abnormal functional stress test and with non-obstructive coronary artery disease (NOCAD) based on demographic data and resting ECG waveforms. Methods This study included 1,893 NOCAD patients (<50% angiographic stenosis) who underwent CMD evaluation as well as a standard ECG up to 1 year prior. Microvascular endothelial-independent dysfunction was defined by abnormal coronary flow reserve (CFR) <2.5 in response to intracoronary adenosine administration. Microvascular endothelial dysfunction was defined by a maximal percent increase in coronary blood flow (%ΔCBF) ≤50% in response to intracoronary acetylcholine infusion. We trained algorithms to distinguish between the following outcomes: CFR ≤2.5, ΔCBF (%) ≤50, and the combination of both. Two classes of algorithms were trained, one depending on ECG waveforms as input, and another using tabular style clinical data. The optimal classification threshold was determined by maximizing Youden's J. Results Mean age was 51±12 years and 66% were females (n=1,257). AUC values ranged from 0.49 to 0.67 for all the outcomes. The best performance in our analysis was for the outcome CFR ≤2.5 via logistic regression on tabular variables. AUC and accuracy were 0.67 and 60%; while sensitivity and NPV were 70% and 85%. Specificity and PPV were 56% and 0.35%. When decreasing the threshold from the “optimal” one (24%) to 15%, sensitivity and NPV increased to 92% and 90% respectively, while specificity and PPV decreased to 25% and 29% respectively (Figure 2). Conclusion An AI-enabled algorithm may be able to assist clinical guidance by ruling out CMD in patients presenting with chest pain and/or an abnormal functional stress test. This algorithm needs to be prospectively validated in different cohorts. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The James Nutter Family & Maria Long Family Fellowship in Cardiovascular Research and Mayo Clinic Figure 1Figure 2
Detecting cardiomyopathies in pregnancy and the postpartum period using ECG
Abstract Background Cardiovascular disease (CVD) has been identified as a major threat to maternal health in the US and UK with cardiomyopathy being one of the most common acquired CVD in the pregnant and postpartum period. Diagnosing cardiomyopathy in pregnancy is challenging due to an overlap of cardiovascular symptoms with normal pregnancy symptoms. Purpose The purpose of this study was to evaluate the effectiveness of an ECG based deep learning model in identifying cardiomyopathy among pregnant and postpartum women. Methods We utilized an ECG based deep learning model to detect cardiomyopathy in a cohort of pregnant or postpartum women seen at multiple hospital sites. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters. Results 1,807 women were included. 7%, 10% and 13% had LVEF ≤35%, <45% and <50% respectively. The ECG based deep learning model identified cardiomyopathy with an AUC of 0.92 for left ventricular ejection fraction (LVEF) ≤35%, 0.89 for LVEF <45% and 0.87 for LVEF <50%. For LVEF ≤35%, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to white (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 and 0.72 respectively. Conclusions A deep learning model effectively identifies cardiomyopathy in pregnant or postpartum women, outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This study was made possible using resources supported by the Mayo Clinic Women's Health Research Center and the Mayo Clinic Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program funded by the National Institutes of Health (NIH), grant number K12 HD065987. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Machine learning aids clinical decision-making in patients presenting with angina and non-obstructive coronary artery disease
Abstract Aims The current gold standard comprehensive assessment of coronary microvascular dysfunction (CMD) is through a limited-access invasive catheterization lab procedure. We aimed to develop a point-of-care tool to assist clinical guidance in patients presenting with chest pain and/or an abnormal cardiac functional stress test and with non-obstructive coronary artery disease (NOCAD). Methods and results This study included 1893 NOCAD patients (<50% angiographic stenosis) who underwent CMD evaluation as well as an electrocardiogram (ECG) up to 1-year prior. Endothelial-independent CMD was defined by coronary flow reserve (CFR) ≤2.5 in response to intracoronary adenosine. Endothelial-dependent CMD was defined by a maximal percent increase in coronary blood flow (%ΔCBF) ≤50% in response to intracoronary acetylcholine infusion. We trained algorithms to distinguish between the following outcomes: CFR ≤2.5, %ΔCBF ≤50, and the combination of both. Two classes of algorithms were trained, one depending on ECG waveforms as input, and another using tabular clinical data. Mean age was 51 ± 12 years and 66% were females (n = 1257). Area under the curve values ranged from 0.49 to 0.67 for all the outcomes. The best performance in our analysis was for the outcome CFR ≤2.5 with clinical variables. Area under the curve and accuracy were 0.67% and 60%. When decreasing the threshold of positivity, sensitivity and negative predictive value increased to 92% and 90%, respectively, while specificity and positive predictive value decreased to 25% and 29%, respectively. Conclusion An artificial intelligence-enabled algorithm may be able to assist clinical guidance by ruling out CMD in patients presenting with chest pain and/or an abnormal functional stress test. This algorithm needs to be prospectively validated in different cohorts.
Artificial Intelligence‐Enhanced ECG Identification of Low Ejection Fraction: A Pragmatic, Cluster‐Randomized Clinical Trial
Research ObjectiveAn artificial intelligence (AI) algorithm based on ECG was integrated into clinical workflows to identify patients with a high likelihood of low ejection (EF), a condition that is underdiagnosed but treatable. The trial aimed to assess whether the AI‐powered clinical decision support enabled early diagnosis of low EF.Study DesignA pragmatic, cluster randomized controlled trial (RCT) was conducted in 45 primary care practices, including an academic medical center as well as community and rural clinics across Minnesota and Wisconsin. A total of 120 primary care teams, including 358 clinicians, were randomized to either intervention (access to AI results with positive results indicating a high likelihood of low EF; 181 clinicians) or control (usual care; 177 clinicians). The primary endpoint was a new diagnosis of EF≤50% within 90 days. A positive deviance qualitative study and a survey were used to assess implementation strategies.Population StudiedIn total, 22,641 adult patients (N = 11,573 intervention; N = 11,068 control) with ECG performed as part of routine care between 8/5/2019 and 3/31/2020 were included. Patients were excluded if they had known EF≤50% or a history of documented heart failure (HF) identified by clinical notes abstracted by natural language processing.Principal FindingsThe mean age of patients was 60.5 ± 17.6 years; 53.9% were women. Positive AI results were found in 6.0% of patients in both arms. Clinicians in the intervention group obtained more echocardiograms for patients with positive results (38.1% control vs. 49.6% intervention, p < 0.001), but in the overall cohort, the echocardiogram utilization was similar (18.2% vs. 19.2%, p = 0.17). The intervention increased the diagnosis of low EF in the overall cohort (1.6% vs. 2.1%, odds ratio [OR] 1.32 [1.01–1.61], p = 0.007) and among patients with positive results (14.5% vs. 19.5% OR 1.43 [1.08–1.91], p = 0.01). Results using different thresholds for low EF were consistent with the primary result. Among patients with positive results, the intervention increased echocardiography more significantly in women vs. men (p for interaction 0.02), in patients without prior echocardiogram vs. those with prior echocardiogram (p for interaction 0.04), and in patients whose ECGs were ordered in outpatient clinics (p for interaction 0.02).ConclusionsAn AI algorithm run on existing ECGs enabled the early diagnosis of low EF in a large cohort of patients managed in routine primary care practices. Because ECG is a low‐cost test frequently performed for a variety of purposes, the algorithm could improve early diagnosis and treatment of a condition that is often asymptomatic but has effective treatments, and thus, reduce the disease burden in broad populations.Implications for Policy or PracticeThe current study is one of the first RCTs that demonstrated the value of AI in routine practice. Low EF confers an increased risk of HF progression and mortality. Although there are effective therapies, low EF is undiagnosed, leading to missed opportunities for treatment. EF can be readily determined by echocardiography, but the imagining test is too resource‐intensive to screen unselected populations. The AI applied to the existing ECGs could identify high‐risk patients for further assessment.Primary Funding SourceMayo Clinic.
Application of artificial intelligence to the electrocardiogram
Abstract Artificial intelligence (AI) has given the electrocardiogram (ECG) and clinicians reading them super-human diagnostic abilities. Trained without hard-coded rules by finding often subclinical patterns in huge datasets, AI transforms the ECG, a ubiquitous, non-invasive cardiac test that is integrated into practice workflows, into a screening tool and predictor of cardiac and non-cardiac diseases, often in asymptomatic individuals. This review describes the mathematical background behind supervised AI algorithms, and discusses selected AI ECG cardiac screening algorithms including those for the detection of left ventricular dysfunction, episodic atrial fibrillation from a tracing recorded during normal sinus rhythm, and other structural and valvular diseases. The ability to learn from big data sets, without the need to understand the biological mechanism, has created opportunities for detecting non-cardiac diseases as COVID-19 and introduced challenges with regards to data privacy. Like all medical tests, the AI ECG must be carefully vetted and validated in real-world clinical environments. Finally, with mobile form factors that allow acquisition of medical-grade ECGs from smartphones and wearables, the use of AI may enable massive scalability to democratize healthcare.
Detecting cardiomyopathies in pregnancy and the postpartum period with an electrocardiogram-based deep learning model
Abstract Aims Cardiovascular disease is a major threat to maternal health, with cardiomyopathy being among the most common acquired cardiovascular diseases during pregnancy and the postpartum period. The aim of our study was to evaluate the effectiveness of an electrocardiogram (ECG)-based deep learning model in identifying cardiomyopathy during pregnancy and the postpartum period. Methods and results We used an ECG-based deep learning model to detect cardiomyopathy in a cohort of women who were pregnant or in the postpartum period seen at Mayo Clinic. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters. The study cohort included 1807 women; 7%, 10%, and 13% had left ventricular ejection fraction (LVEF) of 35% or less, <45%, and <50%, respectively. The ECG-based deep learning model identified cardiomyopathy with AUCs of 0.92 (LVEF ≤ 35%), 0.89 (LVEF < 45%), and 0.87 (LVEF < 50%). For LVEF of 35% or less, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to White (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 to 0.86 and 0.72, respectively. Conclusions An ECG-based deep learning model effectively identifies cardiomyopathy during pregnancy and the postpartum period and outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting.
Coronary Microvascular Dysfunction and the Risk of Atrial Fibrillation From an Artificial Intelligence-Enabled Electrocardiogram
Abstract Aims We sought to investigate whether artificial intelligence (AI) and specifically deep neural networks (NNs) for electrocardiogram (ECG) signal analysis can be explained using human-selected features. We also sought to quantify such explainability and test if the AI model learns features that are similar to a human expert. Methods and results We used a set of 100 000 ECGs that were annotated by human explainable features. We applied both linear and non-linear models to predict published ECG AI models output for the detection of patients’ age and sex. We further used canonical correlation analysis to quantify the amount of shared information between the NN features and human-selected features. We reconstructed single human-selected ECG features from the unexplained NN features using a simple linear model. We noticed a strong correlation between the simple models and the AI output (R2 of 0.49–0.57 for the linear models and R2 of 0.69–0.70 for the non-linear models). We found that the correlation of the human explainable features with either 13 of the strongest age AI features or 15 of the strongest sex AI features was above 0.85 (for comparison, the first 14 principal components explain 90% of the human feature variance). We linearly reconstructed single human-selected ECG features from the AI features with R2 up to 0.86. Conclusion This work shows that NNs for ECG signals extract features in a similar manner to human experts and that they also generate additional novel features that help achieve superior performance.
Abstract 14368: Artificial Intelligence-Electrocardiography to Predict Time to Atrial Fibrillation: An Analysis of Mayo Clinic Study of Aging
Introduction: An artificial intelligence (AI) algorithm applied to electrocardiography (ECG) during normal sinus rhythm (NSR) has been shown to predict concomitant atrial fibrillation (AF). We sought to characterize the value of AI-ECG as a predictor of future AF and assess its performance compared to other clinical prediction scores in a population-based sample. Methods: We calculated the AI-ECG probability during NSR in patients who enrolled in the population-based Mayo Clinic Study of Aging with at least one ECG in NSR within two years prior and no history of AF at the time of the baseline study visit. The cumulative incidence of AF was estimated for strata defined by AI-ECG probability and CHARGE-AF score. Cox proportional hazards were fit to assess the independent prognostic value and interaction of AI-ECG probability and CHARGE-AF score. Concordance (c) statistics were calculated for AI-ECG probability, CHARGE-AF score and combined AI-ECG and CHARGE-AF score. Results: A total of 1,936 patients with a median age 75.8 (quartile range [QR] 70.4, 81.8) years, median CHARGE-AF score 14.0 (QR 13.2, 14.7) and median CHADS2VASC score 3 (QR 2, 4) were included in the analysis. The cumulative incidence of AF increased in a stepwise fashion across quartiles of AI-ECG probability and CHARGE-AF score (Figure 1). When compared in the same model, both AI-ECG probability (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.51-2.04) and CHARGE-AF score (HR 1.90, 95% CI 1.58-2.28) independently predicted AF without significant interaction (p=0.54). C statistics were 0.69 (95% CI 0.66-0.72) for AI-ECG probability, 0.69 (95% CI 0.66-0.71) for CHARGE-AF and 0.72 (95% CI 0.69-0.75) for combined AI-ECG and CHARGE-AF score. Conclusions: In the Mayo Clinic Study of Aging, both the AI-ECG probability and CHARGE-AF score independently predicted time to AF. The AI-ECG may offer a means to assess risk with a single test without requiring manual or automated clinical data abstraction.