Non-Invasive Electrocardiographic Mapping of Arrhythmia and Arrhythmogenic substrate in the Human Ventricle.

PhD Theses.The ablation of ventricular tachycardia often involves mapping when the arrhythmia is ongoing. This is often limited by haemodynamic instability. Non-invasive electrocardiographic mapping (ECGI) may aid in the mapping process by allowing expedient localisation. However, insufficient testing of this technology against ground truth data has been conducted. Furthermore, the system could have utility in detection of arrhythmogenic substrate. Current clinical practice uses echocardiography to risk stratify patients for implantation of intracardiac defibrillators (ICDs). Invasive epicardial electrogram data was collected in 8 patients. Activation and repolarisation times were compared to ECGI derived data showing modest correlation. A detailed analysis of ventricular tachycardia sites of origin in the heart was elucidated using validated electrophysiological techniques. These were compared to ECGI derived data in 18 patients, showing better accuracy than the 12 lead ECG with a resolution of ~2.2cm suggesting it may be a useful adjunctive tool in mapping unstable VT. ECGI derived data collected during sinus rhythm was compared to invasive electrogram maps in 16 patients. The capacity of ECGI to localise scar showed modest accuracy. ECGI and Cardiac MRI scans were performed in 21 patients with cardiac amyloidosis. ECGI showed cardiac amyloidosis to be associated with both ventricular conduction and repolarization abnormalities, supporting the hypothesis that arrhythmic mechanisms may be linked to mortality in this condition

Limitations and Challenges in Mapping Ventricular Tachycardia: New Technologies and Future Directions

Recurrent episodes of ventricular tachycardia in patients with structural heart disease are associated with increased mortality and morbidity, despite the life-saving benefits of implantable cardiac defibrillators. Reducing implantable cardiac defibrillator therapies is important, as recurrent shocks can cause increased myocardial damage and stunning, despite the conversion of ventricular tachycardia/ventricular fibrillation. Catheter ablation has emerged as a potential therapeutic option either for primary or secondary prevention of these arrhythmias, particularly in post-myocardial infarction cases where the substrate is well defined. However, the outcomes of catheter ablation of ventricular tachycardia in structural heart disease remain unsatisfactory in comparison with other electrophysiological procedures. The disappointing efficacy of ventricular tachycardia ablation in structural heart disease is multifactorial. In this review, we discuss the issues surrounding this and examine the limitations of current mapping approaches, as well as newer technologies that might help address them

Validation and Opportunities of Electrocardiographic Imaging: From Technical chievements to Clinical Applications

[EN] Electrocardiographic imaging (ECGI) reconstructs the electrical activity of the heart from a dense array of body-surface electrocardiograms and a patient-specific heart-torso geometry. Depending on how it is formulated, ECGI allows the reconstruction of the activation and recovery sequence of the heart, the origin of premature beats or tachycardia, the anchors/hotspots of re-entrant arrhythmias and other electrophysiological quantities of interest. Importantly, these quantities are directly and non-invasively reconstructed in a digitized model of the patient's three-dimensional heart, which has led to clinical interest in ECGI's ability to personalize diagnosis and guide therapy. Despite considerable development over the last decades, validation of ECGI is challenging. Firstly, results depend considerably on implementation choices, which are necessary to deal with ECGI's ill-posed character. Secondly, it is challenging to obtain (invasive) ground truth data of high quality. In this review, we discuss the current status of ECGI validation as well as the major challenges remaining for complete adoption of ECGI in clinical practice. Specifically, showing clinical benefit is essential for the adoption of ECGI. Such benefit may lie in patient outcome improvement, workflow improvement, or cost reduction. Future studies should focus on these aspects to achieve broad adoption of ECGI, but only after the technical challenges have been solved for that specific application/pathology. We propose 'best' practices for technical validation and highlight collaborative efforts recently organized in this field. Continued interaction between engineers, basic scientists, and physicians remains essential to find a hybrid between technical achievements, pathological mechanisms insights, and clinical benefit, to evolve this powerful technique toward a useful role in clinical practice.This study received financial support from the Hein Wellens Fonds, the Cardiovascular Research and Training Institute (CVRTI), the Nora Eccles Treadwell Foundation, the National Institute of General Medical Sciences of the National Institutes of Health (P41GM103545), the National Institutes of Health (NIH HL080093), the French government as part of the Investments of the Future program managed by the National Research Agency (ANR-10-IAHU-04), from the VEGA Grant Agency in Slovakia (2/0071/16), from the Slovak Research and Development Agency (APVV-14-0875), the Fondo Europeo de Desarrollo Regional (FEDER), the Instituto de Salud Carlos III (PI17/01106) and from Conselleria d'Educacio, Investigacio, Cultura i Esport de la Generalitat Valenciana (AICO/2018/267) and NIH grant (HL125998) and National Science Foundation (ACI-1350374).Cluitmans, M.; Brooks, D.; Macleod, RS.; Dossel, O.; Guillem Sánchez, MS.; Van Dam, P.; Svehlikova, J.... 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Towards enabling cardiac digital twins of myocardial infarction using deep computational models for inverse inference

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 myocardial infarction (MI). The inference of accurate myocardial tissue properties is crucial in creating a reliable CDT of MI. In this work, we investigate the feasibility of inferring myocardial tissue properties from the electrocardiogram (ECG) within a CDT platform. 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 present a novel deep computational model, comprising a dual-branch variational autoencoder and an inference model, to infer infarct location and distribution from the simulated QRS. The proposed model achieves mean Dice scores of 0.457 ± 0.317 and 0.302 ± 0.273 for the inference of left ventricle scars and border zone, respectively. The sensitivity analysis enhances our understanding of the complex relationship between infarct characteristics and electrophysiological features. The in silico experimental results show that the model can effectively capture the relationship for the inverse inference, with promising potential for clinical application in the future. The code is available at https: //github.com/lileitech/MI_inverse_inference

Feasibility of improving risk stratification in the inherited cardiac conditions

Fatal ventricular arrhythmias can occur in patients with Hypertrophic Cardiomyopathy, Brugada Syndrome and rarely in patients with normal cardiac investigations. Despite very different pathogeneses, we hypothesised that a common electrophysiological substrate precipitates these arrhythmias and could be used as a marker for risk stratification. In Chapter 3 of this thesis, we found that fewer than half the cardiac arrest survivors with Brugada Syndrome would have been offered prophylactic defibrillators based on current risk scoring, highlighting the need for better risk stratification. Our group previously used a commercially available 252-electrode vest which constructs ventricular electrograms onto a CT image of the heart to show exercise related differences in high-risk patients. In Chapter 4, we applied this method to Brugada patients, but could not reproduce prior results. Further investigation revealed periodic changes in activation patterns after exercise that could explain this discrepancy. An alternative matrix approach was developed to overcome this problem. Exercise induced conduction heterogeneity differentiated Brugada patients from unaffected controls, but not those surviving cardiac arrest. However, if considered alongside spontaneous type 1 ECG and syncope, inducible conduction heterogeneity markedly improved identification of Brugada cardiac arrest survivors. In Chapter 5 the method was shown to differentiate idiopathic ventricular fibrillation patients from those fully recovered from acute ischaemic cardiac arrest, implying a permanent electrophysiological abnormality. In Chapter 8, we showed prolonged mean local activation times and activation-recovery intervals in hypertrophic cardiomyopathy cardiac arrest survivors compared to those without previous ventricular arrhythmia. These metrics were combined into both logistic regression and support vector machine models to strongly differentiate the groups. We concluded that electrophysiological changes could identify cardiac arrest survivors in various cardiac conditions, but a single factor common pathway was not established. Prospective studies are required to determine if using these parameters could enhance current risk stratification for sudden death.Open Acces

Contemporary Management of Complex Ventricular Arrhythmias

Percutaneous catheter ablation is an effective and safe therapy that can eliminate ventricular tachycardia, reducing the risks of both recurrent arrhythmia and shock therapies from a defibrillator. Successful ablation requires accurate identification of arrhythmic substrate and the effective delivery of energy to the targeted tissue. A thorough pre-procedural assessment is needed before considered 3D electroanatomical mapping can be performed. In contemporary practice, this must combine traditional electrophysiological techniques, such as activation and entrainment mapping, with more novel physiological mapping techniques for which there is an ever-increasing evidence base. Novel techniques to maximise energy delivery to the tissue must also be considered and balanced against their associated risks of complication. This review provides a comprehensive appraisal of contemporary practice and the evidence base that supports recent developments in mapping and ablation, while also considering potential future developments in the field

Personalized Multi-Scale Modeling of the Atria: Heterogeneities, Fiber Architecture, Hemodialysis and Ablation Therapy

This book targets three fields of computational multi-scale cardiac modeling. First, advanced models of the cellular atrial electrophysiology and fiber orientation are introduced. Second, novel methods to create patient-specific models of the atria are described. Third, applications of personalized models in basic research and clinical practice are presented. The results mark an important step towards the patient-specific model-based atrial fibrillation diagnosis, understanding and treatment

Contemporary Management of Complex Ventricular Arrhythmias

Percutaneous catheter ablation is an effective and safe therapy that can eliminate ventricular tachycardia, reducing the risks of both recurrent arrhythmia and shock therapies from a defibrillator. Successful ablation requires accurate identification of arrhythmic substrate and the effective delivery of energy to the targeted tissue. A thorough pre-procedural assessment is needed before considered 3D electroanatomical mapping can be performed. In contemporary practice, this must combine traditional electrophysiological techniques, such as activation and entrainment mapping, with more novel physiological mapping techniques for which there is an ever-increasing evidence base. Novel techniques to maximise energy delivery to the tissue must also be considered and balanced against their associated risks of complication. This review provides a comprehensive appraisal of contemporary practice and the evidence base that supports recent developments in mapping and ablation, while also considering potential future developments in the field