Digital twinning of cardiac electrophysiology models from the surface ECG: a geodesic backpropagation approach

The eikonal equation has become an indispensable tool for modeling cardiac electrical activation accurately and efficiently. In principle, by matching clinically recorded and eikonal-based electrocardiograms (ECGs), it is possible to build patient-specific models of cardiac electrophysiology in a purely non-invasive manner. Nonetheless, the fitting procedure remains a challenging task. The present study introduces a novel method, Geodesic-BP, to solve the inverse eikonal problem. Geodesic-BP is well-suited for GPU-accelerated machine learning frameworks, allowing us to optimize the parameters of the eikonal equation to reproduce a given ECG. We show that Geodesic-BP can reconstruct a simulated cardiac activation with high accuracy in a synthetic test case, even in the presence of modeling inaccuracies. Furthermore, we apply our algorithm to a publicly available dataset of a rabbit model, with very positive results. Given the future shift towards personalized medicine, Geodesic-BP has the potential to help in future functionalizations of cardiac models meeting clinical time constraints while maintaining the physiological accuracy of state-of-the-art cardiac models.Comment: 9 pages, 5 figure

Shape of my heart: Cardiac models through learned signed distance functions

The efficient construction of an anatomical model is one of the major challenges of patient-specific in-silico models of the human heart. Current methods frequently rely on linear statistical models, allowing no advanced topological changes, or requiring medical image segmentation followed by a meshing pipeline, which strongly depends on image resolution, quality, and modality. These approaches are therefore limited in their transferability to other imaging domains. In this work, the cardiac shape is reconstructed by means of three-dimensional deep signed distance functions with Lipschitz regularity. For this purpose, the shapes of cardiac MRI reconstructions are learned from public databases to model the spatial relation of multiple chambers in Cartesian space. We demonstrate that this approach is also capable of reconstructing anatomical models from partial data, such as point clouds from a single ventricle, or modalities different from the trained MRI, such as electroanatomical mapping, and in addition, allows us to generate new anatomical shapes by randomly sampling latent vectors

Comparison of m-mode echocardiographic left ventricular mass measured using digital and strip chart readings: The Atherosclerosis Risk in Communities (ARIC) study

BACKGROUND: Epidemiological and clinical studies frequently use echocardiography to measure LV wall thicknesses and chamber dimension for estimating quantitative measures of LV mass. While echocardiographic M-mode LV images have traditionally been measured using hand-held calipers and strip-chart paper tracings, digitized M-mode LV image measurements made directly on the computer screen using electronic calipers have become standard practice. We sought to determine if systematic differences in LV mass occur between the two methods by comparing LV mass measured from simultaneous M-mode strip chart recordings and digitized recordings. METHODS: The Atherosclerosis Risk in Communities study applied the latter method. To determine if systematic differences in LV mass occur between the two methods, LV mass was measured from simultaneous M-mode strip chart recordings and digitized recordings. RESULTS: We found no difference in LV mass (p > .25) and a strong correlation in LV mass between the two methods (r = 0.97). Neither age, sex, nor hypertension status affected the correlation of LV mass between the two methods. CONCLUSIONS: We conclude that digital estimates of LV mass provide unbiased estimates comparable to the strip-chart method

Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies

Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates the AP for given maximum conductances of selected ion channels, pumps, and exchangers. Its applicability in pharmacological studies was tested on synthetic and experimental data. The NN emulator potentially enables massive speed-ups compared to regular simulations and the forward problem (find drugged AP for pharmacological parameters defined as scaling factors of control maximum conductances) on synthetic data could be solved with average root-mean-square errors (RMSE) of 0.47 mV in normal APs and of 14.5 mV in abnormal APs exhibiting early afterdepolarizations (72.5% of the emulated APs were alining with the abnormality, and the substantial majority of the remaining APs demonstrated pronounced proximity). This demonstrates not only very fast and mostly very accurate AP emulations but also the capability of accounting for discontinuities, a major advantage over existing emulation strategies. Furthermore, the inverse problem (find pharmacological parameters for control and drugged APs through optimization) on synthetic data could be solved with high accuracy shown by a maximum RMSE of 0.22 in the estimated pharmacological parameters. However, notable mismatches were observed between pharmacological parameters estimated from experimental data and distributions obtained from the Comprehensive in vitro Proarrhythmia Assay initiative. This reveals larger inaccuracies which can be attributed particularly to the fact that small tissue preparations were studied while the emulator was trained on single cardiomyocyte data. Overall, our study highlights the potential of NN emulators as powerful tool for an increased efficiency in future quantitative systems pharmacology studies

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

Domestic elites and external actors in post-conflict democratisation: mapping interactions and their impact

Following the end of the Cold War, post-conflict democratisation has rarely occurred without a significant international involvement. This contribution argues that an explanation of the outcomes of post-conflict democratisation requires more than an examination of external actors, their mission mandates or their capabilities and deficiencies. In addition, there is a need to study domestic elites, their preferences and motivations, as well as their perceptions of and their reactions to external interference. Moreover, the patterns of external–internal interactions may explain the trajectory of state-building and democracy promotion efforts. These issues deserve more attention from both scholars and practitioners in the fields of peace- and state-building, democracy promotion, regime transition and elite research. Analyses of external actors and domestic elites in post-conflict democratisation should therefore address three principal issues: (1) the identification of relevant domestic elites in externally induced or monitored state-building and democratisation processes, (2) the dynamics of external–domestic interactions and (3) the impact of these interactions on the outcomes of post-conflict democratisation

Phantom Borders in Eastern Europe

This paper is programmatic: it defines the concept of “phantom borders” and describes its heuristic potential. The proposed approach positions itself between structuralist methodologies that postulate stable social and cultural regional structures and deconstructive viewpoints that reject the former, while focusing on the discursive dimension of regions. The paper takes this tension as its point of departure. Viewed from a situational perspective, phantom borders are neither to be understood as immutable structures nor as purely discursive constructions, but rather as an outcome of the interaction between three interwoven levels, which are simultaneously: 1) imagined in mental maps and discourses, 2) experienced and perceived by the respective actors, and 3) shaped by everyday practices and continuously updated and implemented. Phantom borders are context sensitive. We argue that the topic of phantom borders is not only relevant for research on eastern Europe, but also for research in “new area studies” in general.Peer Reviewe

GEASI: Geodesic-based earliest activation sites identification in cardiac models

The identification of the initial ventricular activation sequence is a critical step for the correct personalization of patient- specific cardiac models. In healthy conditions, the Purkinje network is the main source of the electrical activation, but under pathological conditions the so-called earliest activation sites (EASs) are possibly sparser and more localized. Yet, their number, location and timing may not be easily inferred from remote recordings, such as the epicardial activation or the 12-lead electrocardiogram (ECG), due to the underlying complexity of the model. In this work, we introduce GEASI (Geodesic-based Earliest Activation Sites Identification) as a novel approach to simultaneously identify all EASs. To this end, we start from the anisotropic eikonal equation modeling cardiac electrical activation and exploit its Hamilton–Jacobi formulation to minimize a given objective function, for example, the quadratic mismatch to given activation measurements. This versatile approach can be extended to estimate the number of activation sites by means of the topological gradient, or fitting a given ECG. We conducted various experiments in 2D and 3D for in-silico models and an in-vivo intracardiac recording collected from a patient undergoing cardiac resynchronization therapy. The results demonstrate the clinical applicability of GEASI for potential future personalized models and clinical intervention

A systematic literature review of simulation models for non-technical skill training in healthcare logistics

Abstract Background Resource allocation in patient care relies heavily on individual judgements of healthcare professionals. Such professionals perform coordinating functions by managing the timing and execution of a multitude of care processes for multiple patients. Based on advances in simulation, new technologies that could be used for establishing realistic representations have been developed. These simulations can be used to facilitate understanding of various situations, coordination training and education in logistics, decision-making processes, and design aspects of the healthcare system. However, no study in the literature has synthesized the types of simulations models available for non-technical skills training and coordination of care. Methods A systematic literature review, following the PRISMA guidelines, was performed to identify simulation models that could be used for training individuals in operative logistical coordination that occurs on a daily basis. This article reviewed papers of simulation in healthcare logistics presented in the Web of Science Core Collections, ACM digital library, and JSTOR databases. We conducted a screening process to gather relevant papers as the knowledge foundation of our literature study. The screening process involved a query-based identification of papers and an assessment of relevance and quality. Results Two hundred ninety-four papers met the inclusion criteria. The review showed that different types of simulation models can be used for constructing scenarios for addressing different types of problems, primarily for training and education sessions. The papers identified were classified according to their utilized paradigm and focus areas. (1) Discrete-event simulation in single-category and single-unit scenarios formed the most dominant approach to developing healthcare simulations and dominated all other categories by a large margin. (2) As we approached a systems perspective (cross-departmental and cross-institutional), discrete-event simulation became less popular and is complemented by system dynamics or hybrid modeling. (3) Agent-based simulations and participatory simulations have increased in absolute terms, but the share of these modeling techniques among all simulations in this field remains low. Conclusions An extensive study analyzing the literature on simulation in healthcare logistics indicates a growth in the number of examples demonstrating how simulation can be used in healthcare settings. Results show that the majority of studies create situations in which non-technical skills of managers, coordinators, and decision makers can be trained. However, more system-level and complex system-based approaches are limited and use methods other than discrete-event simulation