Caroline Mendonça Costa

• PhD
• Research Associate at King's College London

Ventricular arrhythmias (VA) in patients with myocardial infarction (MI) are thought to be associated with structural and electrophysiological remodeling within the infarct border zone (BZ). Personalized computational models have been used to investigate the potential role of the infarct BZ in arrhythmogenesis, which still remains incompletely unde...

Background: Cardiac resynchronization therapy (CRT) increases the risk of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) when the left ventricular (LV) epicardial lead is implanted in proximity to scar. Objective: To determine the mechanisms underpinning this risk, we investigate the effects of pacing on local electrop...

Objective: Interstitial fibrosis is a pathological expansion of the heart's inter-cellular collagen matrix. It is a potential complication of nonischemic cardiomyopathy (NICM), a class of diseases involving electrical and or mechanical dysfunction of cardiac tissue not caused by atherosclerosis. Patients with NICM and interstitial fibrosis often s...

Background Epicardial pacing increases risk of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) when pacing in proximity to scar. Endocardial pacing may be less arrhythmogenic as it preserves the physiological sequence of activation and repolarization. Objective To determine the relative arrhythmogenic risk of endocardia...

Background Re-entrant ventricular tachycardia may be non-inducible or haemodynamically compromising, requiring assessment of the electrophysiological properties of the myocardium during sinus rhythm (i.e., substrate mapping). Areas of heart tissue with slow conduction can act as a critical isthmus for re-entrant electrical excitation and are a pote...

Computational models for cardiac electro-mechanics have been increasingly used to further understand heart function. Small cohort and single patient computational studies provide useful insight into cardiac pathophysiology and response to therapy. However, these smaller studies have limited capability to capture the high level of anatomical variabi...

Cardiac resynchronization therapy (CRT) is one of the few effective treatments for dyssynchronous heart failure (HF), where heart function is worsened due to an electrical substrate pathology causing delayed left ventricular activation. However, 40–50% of patients do not respond to treatment. In this book chapter, we review cardiac computer models...

Background Post myocardial infarction (MI) ventricles contain fibrotic tissue and may have disrupted electrical properties, both of which predispose to an increased risk of life-threatening arrhythmias. Application of epicardial patches obtained from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a potential long-term th...

Reliable and robust simulation of individual patients using patient-specific models (PSMs) is one of the next frontiers for modeling and simulation (M&S) in healthcare. PSMs, which form the basis of digital twins, can be employed as clinical tools to, for example, assess disease state, predict response to therapy, or optimize therapy. They may also...

Background Thresholding based analysis of late gadolinium enhancement cardiac MRI (LGE-CMR) can create scar maps and identify corridors that might provide a reentrant substrate for ventricular tachycardia (VT). Current recommendations employ a full-width-at-half-maximum approach, effectively classifying areas with a pixel-signal-intensity (PSI) >40...

Catheter ablation is currently the only curative treatment for scar-related ventricular tachycardias (VTs). However, not only are ablation procedures long, with relatively high risk, but success rates are punitively low, with frequent VT recurrence. Personalized in-silico approaches have the opportunity to address these limitations. However, state-...

Application of epicardial patches constructed from human-induced pluripotent stem cell- derived cardiomyocytes (hiPSC-CMs) has been proposed as a long-term therapy to treat scarred hearts post myocardial infarction (MI). Understanding electrical interaction between engineered heart tissue patches (EHT) and host myocardium represents a key step towa...

Background The effect of chronic ischemic scar on repolarization is unclear, with conflicting results from human and animal studies. An improved understanding of electrical remodeling within scar and border zone tissue may enhance substrate-guided ablation techniques for ventricular tachycardia. Computational modeling studies have suggested increas...

Background Computational models of the heart built from cardiac MRI and electrophysiology (EP) data have shown promise for predicting the risk of and ablation targets for myocardial infarction (MI) related ventricular tachycardia (VT), as well as to predict paced activation sequences in heart failure patients. However, most recent studies have reli...

Catheter ablation is currently the only curative treatment for scar-related ventricular tachycardias (VTs). However, not only are ablation procedures long, with relatively high risk, but success rates are punitively low, with frequent VT recurrence. Personalized in-silico approaches have the opportunity to address these limitations. However, state-...

For over 100 years cardiac electrophysiology has been measured in the clinic. The electrical signals that can be measured span from noninvasive ECG and body surface potentials measurements through to detailed invasive measurements of local tissue electrophysiology. These electrophysiological measurements form a crucial component of patient diagnosi...

Motivation: Computational models of the heart are increasingly being used in the development of devices, patient diagnosis and therapy guidance. While software techniques have been developed for simulating single hearts, there remain significant challenges in simulating cohorts of virtual hearts from multiple patients. Dataset Description: We prese...

Funding Acknowledgements WT 203148/Z/16/Z; MR/N011007/1; RE/08/003; PG/15/91/31812; PG/16/81/32441 Background Endocardial pacing has been shown to improve response to cardiac resynchronization therapy (CRT) in comparison to conventional epicardial pacing and the physiological activation, endocardium to epicardium, is proposed to make it less arrhy...

Background Anti‐tachycardia pacing (ATP), which may avoid unnecessary ICD shocks, does not always terminate ventricular arrhythmias (VAs). Mean entropy calculated using cardiac magnetic resonance texture analysis (CMR‐TA) has been shown to predict appropriate ICD therapy. We examined whether scar heterogeneity, quantified by mean entropy, is associ...

Objective: Interstitial fibrosis is a pathological expansion of the heart's inter-cellular collagen matrix. It is a potential complication of nonischemic cardiomyopathy (NICM), a class of diseases involving electrical and or mechanical dysfunction of cardiac tissue not caused by atherosclerosis. Patients with NICM and interstitial fibrosis often su...

Background: Cardiac resynchronization therapy (CRT) is associated with increased risk of ventricular arrhythmias when pacemaker leads are implanted in proximity to a scar. However, the mechanisms leading to this increased risk remain poorly understood. Investigating the role of lead location on arrhythmia risk in the clinical setting is impractical...

Aims: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and as...

Aims: Patients who present with non-ischemic dilated cardiomyopathy (NIDCM) and enhancement on late gadolinium magnetic resonance imaging (LGE-CMR), are at high risk of sudden cardiac death (SCD). Further risk stratification of these patients based on LGE-CMR may be improved through better understanding of fibrosis microstructure. Our aim is to exa...

Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF) patients with an electrical substrate pathology causing ventricular dyssynchrony. However 40–50% of patients do not respond to treatment. Cardiac modeling of the electrophysiology, electromechanics, and hemodynamics of the heart has been used to study mechanism...

Advanced imaging technologies provide a wealth of information on cardiac anatomy and structure at high spatial resolutions (∼300 µm-1 mm), allowing to identify microscopic size scale (< 1 mm) structural discontinuities, which act as a barrier to electrical propagation in the heart. The explicit representation of fine-scale structures results in sig...

Electrical propagation in cardiac tissue is a discrete or discontinuous phenomenon that reflects the complexity of the anatomical structures and their organization in the heart, such as myocytes, gap junctions, microvessels, and extracellular matrix, just to name a few. Discrete models or microscopic and discon- tinuous models are, so far, the best...

We present ideas and first results on a GPU acceleration of a non-linear solver embedded into the biomedical application code CARP. The linear system solvers have been transferred already in the past and so we concentrate on how to extend the GPU acceleration to larger portions of the code. The finite element assembling of stiffness and mass matric...

Advanced medical imaging technologies provide a wealth of information on cardiac anatomy and structure at a paracellular resolution, allowing to identify microstructural discontinuities which disrupt the intracellular matrix. Current state-of-the-art computer models built upon such datasets account for increasingly finer anatomical details, however...

Driven by recent advances in medical imaging, image segmentation and numerical techniques, computer models of ventricular electrophysiology account for increasingly finer levels of anatomical and biophysical detail. However, considering the large number of model parameters involved parameterization poses a major challenge. A minimum requirement in...

Computational modeling of cardiac electrophysiology demands multidisciplinary groups and a growing number of simulation software to validate new models with experimental data. These in silico experiments are very often composed of legacy tools developed by different researchers and based on different technologies. Therefore, they tend to be very ha...

The presence of connective tissue as well as interstitial clefts forms a natural barrier to the electrical propagation in the heart. At a microscopic scale, such uncoupling structures change the pattern of the electrical conduction from uniform towards complex and may play a role in the genesis of cardiac arrhythmias. The anatomical diversity of co...

The cardiac Monodomain model is a mathematical model extensively used in studies of propagation of bioelectric wavefronts in the heart. To be able to use the model for complex and large cardiac simulations, such as the case of whole heart and 3D simulations, some parameters of the model that are known to physiologically vary in space, such as the i...

Cardiac modeling is being used in a variety of ways to support the tests of new drugs, the development of new medical devices and of non-invasive diagnostic techniques. Computer models have become valuable tools for the study and comprehension of the complex phenomena of cardiac electrophysiology. However, the complexity, the multi-scale and multi-...

Cardiac modeling is being used in a variety of ways to support the tests of new drugs, the development of new medical devices and of non-invasive diagnostic techniques. Computer models have become valuable tools for the study and comprehension of the complex phenomena of cardiac electrophysiology. However, the complexity, the multi-scale and multi-...

We developed a computer model for the electrophysiology of cardiac cells from the mouse sinoatrial node. The available biophysical data have been incorporated into the model to quantify the ionic currents verified in these specific group of cardiac cells. The model is based on a previous approach describing the action potential in mouse ventricular...

Chagas’ Disease is an endemic infection in many areas of South and Central America that may cause a fatal type of myocarditis. In the acute phase of the disease, ventricular extrasystoles and tachycardia have been reported. Experiments with cardiac myocytes in the acute stage of Chagas’ Disease have suggested a depression of Ito , the Ca2 + -indepe...