Anatomical basis of sex differences in human post-myocardial infarction ECG phenotypes identified by novel automated torso-cardiac 3D reconstruction

The electrocardiogram (ECG) is routinely used in cardiology, though its interpretation is confounded by anatomical variability. A novel, automated computational pipeline enables quantification of torso-ventricular anatomy metrics from magnetic resonance imaging, and comparison to ECG characteristics. Sex and myocardial infarction differences are investigated based on 1051 healthy and 425 post-MI subjects from UK Biobank. Smaller ventricles in females explain ~50% of shorter QRS durations than in males, and contribute to lower STJ amplitudes in females (also due to more superior and posterior position). In females, torso-ventricular anatomy, particularly from larger BMI, is a stronger modulator of T wave amplitude reductions and left-deviated R axis angles in post-MI than in males. Thus, female MI phenotype is less reflective of pathology, and baseline STJ amplitudes and QRS durations are further from clinical thresholds. Therefore, quantification of anatomical sex-differences and impact on ECG in health and disease is critical to avoid clinical sex-bias.

Towards Enabling Cardiac Digital Twins of Myocardial Infarction Using Deep Computational Models for Inverse Inference

Myocardial infarction (MI) demands precise and swift diagnosis. Cardiac digital twins (CDTs) have the potential to offer individualized evaluation of cardiac function in a non-invasive manner, making them a promising approach for personalized diagnosis and treatment planning of MI. The inference of accurate myocardial tissue properties is crucial in creating a reliable CDT platform, and particularly in the context of studying MI. In this work, we investigate the feasibility of inferring myocardial tissue properties from the electrocardiogram (ECG), focusing on the development of a comprehensive CDT platform specifically designed for MI. The platform integrates multi-modal data, such as cardiac MRI and ECG, to enhance the accuracy and reliability of the inferred tissue properties. We perform a sensitivity analysis based on computer simulations, systematically exploring the effects of infarct location, size, degree of transmurality, and electrical activity alteration on the simulated QRS complex of ECG, to establish the limits of the approach. We subsequently propose a deep computational model to infer infarct location and distribution from the simulated QRS. The in silico experimental results show that our model can effectively capture the complex relationships between the QRS signals and the corresponding infarct regions, with promising potential for clinical application in the future. The code will be released publicly once the manuscript is accepted for publication.

Influence of Myocardial Infarction on QRS Properties: A Simulation Study

The interplay between structural and electrical changes in the heart after myocardial infarction (MI) plays a key role in the initiation and maintenance of arrhythmia. The anatomical and electrophysiological properties of scar, border zone, and normal myocardium modify the electrocardiographic morphology, which is routinely analysed in clinical settings. However, the influence of various MI properties on the QRS is not intuitively predictable.In this work, we have systematically investigated the effects of 17 post-MI scenarios, varying the location, size, transmural extent, and conductive level of scarring and border zone area, on the forward-calculated QRS. Additionally, we have compared the contributions of different QRS score criteria for quantifying post-MI pathophysiology.The propagation of electrical activity in the ventricles is simulated via a Eikonal model on a unified coordinate system.The analysis has been performed on 49 subjects, and the results imply that the QRS is capable of identifying MI, suggesting the feasibility of inversely reconstructing infarct regions from QRS.There exist sensitivity variations of different QRS criteria for identifying 17 MI scenarios, which is informative for solving the inverse problem.

Influence of Myocardial Infraction on QRS Properties: A Simulation Study

The interplay between structural and electrical changes in the heart after myocardial infarction (MI) plays a key role in the initiation and maintenance of arrhythmia. The anatomical and electrophysiological properties of scar, border zone, and normal myocardium modify the electrocardiographic morphology, which is routinely analysed in clinical settings. However, the influence of various MI properties on the QRS is not intuitively predictable.In this work, we have systematically investigated the effects of 17 post-MI scenarios, varying the location, size, transmural extent, and conductive level of scarring and border zone area, on the forward-calculated QRS. Additionally, we have compared the contributions of different QRS score criteria for quantifying post-MI pathophysiology.The propagation of electrical activity in the ventricles is simulated via a Eikonal model on a unified coordinate system.The analysis has been performed on 49 subjects, and the results imply that the QRS is capable of identifying MI, suggesting the feasibility of inversely reconstructing infarct regions from QRS.There exist sensitivity variations of different QRS criteria for identifying 17 MI scenarios, which is informative for solving the inverse problem.

Deep Computational Model for the Inference of Ventricular Activation Properties

Patient-specific cardiac computational models are essential for the efficient realization of precision medicine and in-silico clinical trials using digital twins. Cardiac digital twins can provide non-invasive characterizations of cardiac functions for individual patients, and therefore are promising for the patient-specific diagnosis and therapy stratification. However, current workflows for both the anatomical and functional twinning phases, referring to the inference of model anatomy and parameter from clinical data, are not sufficiently efficient, robust, and accurate. In this work, we propose a deep learning based patient-specific computational model, which can fuse both anatomical and electrophysiological information for the inference of ventricular activation properties, i.e., conduction velocities and root nodes. The activation properties can provide a quantitative assessment of cardiac electrophysiological function for the guidance of interventional procedures. We employ the Eikonal model to generate simulated electrocardiogram (ECG) with ground truth properties to train the inference model, where specific patient information has also been considered. For evaluation, we test the model on the simulated data and obtain generally promising results with fast computational time.

Variational Inference over Non-differentiable Cardiac Simulators using Bayesian Optimization

Performing inference over simulators is generally intractable as their runtime means we cannot compute a marginal likelihood. We develop a likelihood-free inference method to infer parameters for a cardiac simulator, which replicates electrical flow through the heart to the body surface. We improve the fit of a state-of-the-art simulator to an electrocardiogram (ECG) recorded from a real patient.