Aims Out-of-hospital cardiac arrest (OHCA) without return of spontaneous circulation (ROSC) despite conventional resuscitation is common and has poor outcomes. Adding extracorporeal membrane oxygenation (ECMO) to cardiopulmonary resuscitation (extracorporeal-CPR) is increasingly used in an attempt to improve outcomes. Methods and results We analysed a prospective registry of 13 191 OHCAs in the Paris region from May 2011 to January 2018. We compared survival at hospital discharge with and without extracorporeal-CPR and identified factors associated with survival in patients given extracorporeal-CPR. Survival was 8% in 525 patients given extracorporeal-CPR and 9% in 12 666 patients given conventional-CPR (P = 0.91). By adjusted multivariate analysis, extracorporeal-CPR was not associated with hospital survival [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.8–2.1; P = 0.24]. By conditional logistic regression with matching on a propensity score (including age, sex, occurrence at home, bystander CPR, initial rhythm, collapse-to-CPR time, duration of resuscitation, and ROSC), similar results were found (OR, 0.8; 95% CI, 0.5–1.3; P = 0.41). In the extracorporeal-CPR group, factors associated with hospital survival were initial shockable rhythm (OR, 3.9; 95% CI, 1.5–10.3; P = 0.005), transient ROSC before ECMO (OR, 2.3; 95% CI, 1.1–4.7; P = 0.03), and prehospital ECMO implantation (OR, 2.9; 95% CI, 1.5–5.9; P = 0.002). Conclusions In a population-based registry, 4% of OHCAs were treated with extracorporeal-CPR, which was not associated with increased hospital survival. Early ECMO implantation may improve outcomes. The initial rhythm and ROSC may help select patients for extracorporeal-CPR.

The heart rhythm disorder long QT syndrome (LQTS) can result in sudden death in the young or remain asymptomatic into adulthood. The features of the surface electrocardiogram (ECG), a measure of the electrical activity of the heart, can be equally variable in LQTS patients, posing well-described diagnostic dilemmas. Here we report a correlation between QT interval prolongation and T-wave notching in LQTS2 patients and use a novel computational framework to investigate how individual ionic currents, as well as cellular and tissue level factors, contribute to notched T waves. Furthermore, we show that variable expressivity of ECG features observed in LQTS2 patients can be explained by as little as 20% variation in the levels of ionic conductances that contribute to repolarization reserve. This has significant implications for interpretation of whole-genome sequencing data and underlies the importance of interpreting the entire molecular signature of disease in any given individual.

Key points• We used a novel high performance computing approach to conduct a sensitivity analysis of emergent properties of simulated ECGs from a transmural cable of cells.• The rapid delayed rectifier and inward rectifying potassium currents are the primary determinants of the height of the T wave in this system. • T height is correlated with the temporal dispersion of repolarisation in the transmural cable while T peak -T end is correlated with the interval from the time of maximum total rate of repolarisation to the end of repolarisation in the cable of cells.• This study advances our understanding of the molecular basis of T wave morphology and the role of epistatis in the modification of cardiac electrical phenotypes.Abstract Altered function of ion channels in the heart can increase the risk of sudden arrhythmic death. Hundreds of genetic variants exist in these cardiac ion channel genes. The challenge is how to interpret the effects of multiple conductance perturbations on the complex multi-variable cardiac electrical system? In theory, sensitivity analysis can address this question. However, to date this approach has been restricted by computational overheads to analysis of isolated cells, which has limited extrapolation to physiologically relevant scales. The goal of this study was to extend existing sensitivity analyses to electrocardiogram (ECG) signals derived from multicellular systems and quantify the contribution of ionic conductances to emergent properties of the ECG. To achieve this, we have developed a highly parallelised simulation environment using unconventional high performance computing architectures to analyse the emergent electrical properties of a multicellular system. This has permitted the first systematic analysis of the molecular basis of the T wave amplitude, revealing important but distinct roles for delayed rectifier and inward rectifier K + currents. In addition to quantifying how interactions between multiple ion channels influence ECG parameters we show that these sensitivities are dynamic functions of heart rate. This study provides a significant advance in our understanding both of how individual ion conductances define ECG signals and of epistatic modification of cardiac electrical phenotypes. The parallelised simulation environment we have developed removes the computational roadblock that has limited A. Sadrieh and S. A. Mann contributed equally to this work. this approach and so provides the framework for future analysis of more complex tissue and whole organ systems.

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Background: Conflicting data exist regarding the benefit of urgent coronary angiogram and percutaneous coronary intervention (PCI) after sudden cardiac arrest, particularly in the absence of ST-segment elevation. We hypothesized that the type of lesions treated (stable versus unstable) influences the benefit derived from PCI. Methods: Data were taken between May 2011 and 2014 from a prospective registry enrolling all sudden cardiac arrest in Paris and suburbs (6.7 million inhabitants). Patients undergoing emergent coronary angiogram were included. Decision to perform PCI was left to the discretion of local teams. We assessed the impact of emergent PCI on survival at discharge according to whether the treated lesion was angiographically unstable or stable, and we investigated the predictive factors for unstable coronary lesions. Results: Among 9265 sudden cardiac arrests occurring during the study period, 1078 underwent emergent coronary angiogram (median age: 59.6 years, 78.3% males): 463 (42.9%) had an unstable lesion, 253 (23.5%) only stable lesions, and 362 (33.6%) no significant lesions. Emergent PCI was performed in 478 patients (91.4% of unstable and 21.7% of stable lesions). At discharge, PCI of unstable lesions was associated with twice-higher survival rate compared with untreated unstable lesions (47.9% versus 25.6%, P =0.013), while stable lesions PCI did not improve survival (25.5% versus 26.3%, P =1.00). After adjustment, PCI of unstable coronary lesions was independently associated with improved survival (odds ratio, 2.09 [95% CI, 1.42–3.09], P <0.001), contrary to PCI of stable lesions (odds ratio, 0.92 [95% CI. 0.44–1.87], P =0.824). Angina, initial shockable rhythm, ST-segment elevation, and absence of known coronary artery disease were independent predictors of unstable lesions. Conclusions: Emergent PCI of unstable lesions is associated with improved survival after sudden cardiac arrest, contrary to PCI of stable lesions. Accordingly, early PCI should only be performed in patients with unstable lesions. Four factors (chest pain, ST-elevation, absence of coronary artery disease history, and shockable initial rhythm) could help identify patients with unstable lesions who would, therefore, benefit from emergent coronary angiogram.

This chapter describes a novel way of carrying out image analysis, reconstruction and processing tasks using cloud based service provided on the Australian National eResearch Collaboration Tools and Resources (NeCTAR) infrastructure. The toolbox allows users free access to a wide range of useful blocks of functionalities (imaging functions) that can be connected together in workflows allowing creation of even more complex algorithms that can be re-run on different data sets, shared with others or additionally adjusted. The functions given are in the area of cellular imaging, advanced X-ray image analysis, computed tomography and 3D medical imaging and visualisation. The service is currently available on the website www.cloudimaging.net.au .

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