Explainable machine learning for neoplasms diagnosis via electrocardiograms: an externally validated study

Background: Neoplasms remains a leading cause of mortality worldwide, with timely diagnosis being crucial for improving patient outcomes. Current diagnostic methods are often invasive, costly, and inaccessible to many populations. Electrocardiogram (ECG) data, widely available and non-invasive, has the potential to serve as a tool for neoplasms diagnosis by using physiological changes in cardiovascular function associated with neoplastic prescences. Methods: This study explores the application of machine learning models to analyze ECG features for the diagnosis of neoplasms. We developed a pipeline integrating tree-based models with Shapley values for explainability. The model was trained and internally validated and externally validated on a second large-scale independent external cohort to ensure robustness and generalizability. Findings: The results demonstrate that ECG data can effectively capture neoplasms-associated cardiovascular changes, achieving high performance in both internal testing and external validation cohorts. Shapley values identified key ECG features influencing model predictions, revealing established and novel cardiovascular markers linked to neoplastic conditions. This non-invasive approach provides a cost-effective and scalable alternative for the diagnosis of neoplasms, particularly in resource-limited settings. Similarly, useful for the management of secondary cardiovascular effects given neoplasms therapies. Interpretation: This study highlights the feasibility of leveraging ECG signals and machine learning to enhance neoplasms diagnostics. By offering interpretable insights into cardio-neoplasms interactions, this approach bridges existing gaps in non-invasive diagnostics and has implications for integrating ECG-based tools into broader neoplasms diagnostic frameworks, as well as neoplasms therapy management.

Electrocardiogram-based diagnosis of liver diseases: an externally validated and explainable machine learning approach

Background: Liver diseases are a major global health concern, often diagnosed using resource-intensive methods. Electrocardiogram (ECG) data, widely accessible and non-invasive, offers potential as a diagnostic tool for liver diseases, leveraging the physiological connections between cardiovascular and hepatic health. Methods: This study applies machine learning models to ECG data for the diagnosis of liver diseases. The pipeline, combining tree-based models with Shapley values for explainability, was trained, internally validated, and externally validated on an independent cohort, demonstrating robust generalizability. Findings: Our results demonstrate the potential of ECG to derive biomarkers to diagnose liver diseases. Shapley values revealed key ECG features contributing to model predictions, highlighting already known connections between cardiovascular biomarkers and hepatic conditions as well as providing new ones. Furthermore, our approach holds promise as a scalable and affordable solution for liver disease detection, particularly in resource-limited settings. Interpretation: This study underscores the feasibility of leveraging ECG features and machine learning to enhance the diagnosis of liver diseases. By providing interpretable insights into cardiovascular-liver interactions, the approach bridges existing gaps in non-invasive diagnostics, offering implications for broader systemic disease monitoring.

CardioLab: Laboratory Values Estimation and Monitoring from Electrocardiogram Signals -- A Multimodal Deep Learning Approach

Background: Laboratory values are fundamental to medical diagnosis and management, but acquiring these values can be costly, invasive, and time-consuming. While electrocardiogram (ECG) patterns have been linked to certain laboratory abnormalities, the comprehensive modeling of these relationships remains underexplored. Methods: We utilize MIMIC-IV dataset to develop multimodal deep-learning models to demonstrate the feasibility of estimating (real-time) and monitoring (predict at future intervals) laboratory value abnormalities from ECG waveforms, demographics, biometrics, and vital signs. Results: The models exhibit a strong predictive performance with AUROC scores above 0.70 in a statistically significant manner for 23 laboratory values in the estimation setting and up to 26 values in the monitoring setting. Most notably, the accurately predictable values encompassing abnormalities across diverse physiological categories such as cardiac, renal, hematological, metabolic, immunological and coagulation. To name examples, for estimation NTproBNP (>353 pg/mL) with 0.882, whereas for monitoring at 30 minutes Urea nitrogen (<6 mg/dL) with 0.851, at 60 minutes creatinine (<0.5 mg/dL) with 0.85, and at 120 minutes hemoglobin (>17.5 g/dL) with 0.821. Conclusions: This study provides first evidence for the feasibility of using ECG data alongside clinical routine data for the real-time estimation and monitoring of laboratory value abnormalities, which could provide a non-invasive, cost-effective supplement to traditional laboratory testing, with strong implications for enhanced patient monitoring and early intervention. Further validation could facilitate their integration into routine clinical practice.

Estimation of Cardiac and Non-cardiac Diagnosis from Electrocardiogram Features

Introduction: Ensuring timely and accurate diagnosis of medical conditions is paramount for effective patient care. Electrocardiogram (ECG) signals are fundamental for evaluating a patient's cardiac health and are readily available. Despite this, little attention has been given to the remarkable potential of ECG data in detecting non-cardiac conditions. Methods: In our study, we used publicly available datasets (MIMIC-IV-ECG-ICD and ECG-VIEW II) to investigate the feasibility of inferring general diagnostic conditions from ECG features. To this end, we trained a tree-based model (XGBoost) based on ECG features and basic demographic features to estimate a wide range of diagnoses, encompassing both cardiac and non-cardiac conditions. Results: Our results demonstrate the reliability of estimating 23 cardiac as well as 21 non-cardiac conditions above 0.7 AUROC in a statistically significant manner across a wide range of physiological categories. Our findings underscore the predictive potential of ECG data in identifying well-known cardiac conditions. However, even more striking, this research represents a pioneering effort in systematically expanding the scope of ECG-based diagnosis to conditions not traditionally associated with the cardiac system.

MDS-ED: Multimodal Decision Support in the Emergency Department -- a Benchmark Dataset for Diagnoses and Deterioration Prediction in Emergency Medicine

Background: Benchmarking medical decision support algorithms often struggles due to limited access to datasets, narrow prediction tasks, and restricted input modalities. These limitations affect their clinical relevance and performance in high-stakes areas like emergency care, complicating replication, validation, and improvement of benchmarks. Methods: We introduce a dataset based on MIMIC-IV, benchmarking protocol, and initial results for evaluating multimodal decision support in the emergency department (ED). We use diverse data modalities from the first 1.5 hours of patient arrival, including demographics, biometrics, vital signs, lab values, and electrocardiogram waveforms. We analyze 1443 clinical labels across two contexts: predicting diagnoses with ICD-10 codes and forecasting patient deterioration. Results: Our multimodal diagnostic model achieves an AUROC score over 0.8 in a statistically significant manner for 357 out of 1428 conditions, including cardiac issues like myocardial infarction and non-cardiac conditions such as renal disease and diabetes. The deterioration model scores above 0.8 in a statistically significant manner for 13 out of 15 targets, including critical events like cardiac arrest and mechanical ventilation, ICU admission as well as short- and long-term mortality. Incorporating raw waveform data significantly improves model performance, which represents one of the first robust demonstrations of this effect. Conclusions: This study highlights the uniqueness of our dataset, which encompasses a wide range of clinical tasks and utilizes a comprehensive set of features collected early during the emergency after arriving at the ED. The strong performance, as evidenced by high AUROC scores across diagnostic and deterioration targets, underscores the potential of our approach to revolutionize decision-making in acute and emergency medicine.

CardioLab: Laboratory Values Estimation from Electrocardiogram Features -- An Exploratory Study

Introduction: Laboratory value represents a cornerstone of medical diagnostics, but suffers from slow turnaround times, and high costs and only provides information about a single point in time. The continuous estimation of laboratory values from non-invasive data such as electrocardiogram (ECG) would therefore mark a significant frontier in healthcare monitoring. Despite its transformative potential, this domain remains relatively underexplored within the medical community. Methods: In this preliminary study, we used a publicly available dataset (MIMIC-IV-ECG) to investigate the feasibility of inferring laboratory values from ECG features and patient demographics using tree-based models (XGBoost). We define the prediction task as a binary prediction problem of predicting whether the lab value falls into low or high abnormalities. The model performance can then be assessed using AUROC. Results: Our findings demonstrate promising results in the estimation of laboratory values related to different organ systems based on a small yet comprehensive set of features. While further research and validation are warranted to fully assess the clinical utility and generalizability of ECG-based estimation in healthcare monitoring, our findings lay the groundwork for future investigations into approaches to laboratory value estimation using ECG data. Such advancements hold promise for revolutionizing predictive healthcare applications, offering faster, non-invasive, and more affordable means of patient monitoring.

CausalConceptTS: Causal Attributions for Time Series Classification using High Fidelity Diffusion Models

Despite the excelling performance of machine learning models, understanding the decisions of machine learning models remains a long-standing goal. While commonly used attribution methods in explainable AI attempt to address this issue, they typically rely on associational rather than causal relationships. In this study, within the context of time series classification, we introduce a novel framework to assess the causal effect of concepts, i.e., predefined segments within a time series, on specific classification outcomes. To achieve this, we leverage state-of-the-art diffusion-based generative models to estimate counterfactual outcomes. Our approach compares these causal attributions with closely related associational attributions, both theoretically and empirically. We demonstrate the insights gained by our approach for a diverse set of qualitatively different time series classification tasks. Although causal and associational attributions might often share some similarities, in all cases they differ in important details, underscoring the risks associated with drawing causal conclusions from associational data alone. We believe that the proposed approach is widely applicable also in other domains, particularly where predefined segmentations are available, to shed some light on the limits of associational attributions.

Cardiac and extracardiac discharge diagnosis prediction from emergency department ECGs using deep learning

Current deep learning algorithms designed for automatic ECG analysis have exhibited notable accuracy. However, akin to traditional electrocardiography, they tend to be narrowly focused and typically address a singular diagnostic condition. In this study, we specifically demonstrate the capability of a single model to predict a diverse range of both cardiac and non-cardiac discharge diagnoses based on a sole ECG collected in the emergency department. Among the 1,076 hierarchically structured ICD codes considered, our model achieves an AUROC exceeding 0.8 in 439 of them. This underscores the models proficiency in handling a wide array of diagnostic scenarios. We emphasize the potential of utilizing this model as a screening tool, potentially integrated into a holistic clinical decision support system for efficiently triaging patients in the emergency department. This research underscores the remarkable capabilities of comprehensive ECG analysis algorithms and the extensive range of possibilities facilitated by the open MIMIC-IV-ECG dataset. Finally, our data may play a pivotal role in revolutionizing the way ECG analysis is performed, marking a significant advancement in the field.

Uncovering ECG Changes during Healthy Aging using Explainable AI

Cardiovascular diseases remain the leading global cause of mortality. This necessitates a profound understanding of heart aging processes to diagnose constraints in cardiovascular fitness. Traditionally, most of such insights have been drawn from the analysis of electrocardiogram (ECG) feature changes of individuals as they age. However, these features, while informative, may potentially obscure underlying data relationships. In this paper, we employ a deep-learning model and a tree-based model to analyze ECG data from a robust dataset of healthy individuals across varying ages in both raw signals and ECG feature format. Explainable AI techniques are then used to identify ECG features or raw signal characteristics are most discriminative for distinguishing between age groups. Our analysis with tree-based classifiers reveal age-related declines in inferred breathing rates and identifies notably high SDANN values as indicative of elderly individuals, distinguishing them from younger adults. Furthermore, the deep-learning model underscores the pivotal role of the P-wave in age predictions across all age groups, suggesting potential changes in the distribution of different P-wave types with age. These findings shed new light on age-related ECG changes, offering insights that transcend traditional feature-based approaches.

Diffusion-based Conditional ECG Generation with Structured State Space Models

Synthetic data generation is a promising solution to address privacy issues with the distribution of sensitive health data. Recently, diffusion models have set new standards for generative models for different data modalities. Also very recently, structured state space models emerged as a powerful modeling paradigm to capture long-term dependencies in time series. We put forward SSSD-ECG, as the combination of these two technologies, for the generation of synthetic 12-lead electrocardiograms conditioned on more than 70 ECG statements. Due to a lack of reliable baselines, we also propose conditional variants of two state-of-the-art unconditional generative models. We thoroughly evaluate the quality of the generated samples, by evaluating pretrained classifiers on the generated data and by evaluating the performance of a classifier trained only on synthetic data, where SSSD-ECG clearly outperforms its GAN-based competitors. We demonstrate the soundness of our approach through further experiments, including conditional class interpolation and a clinical Turing test demonstrating the high quality of the SSSD-ECG samples across a wide range of conditions.