"Recent data show that 7.6 million Americans have survived a myocardial infarction (MI), and 5.1 million Americans suffer from severe heart failure. Stem cell therapy has the potential to improve cardiac function after MI. Two promising cells for cardiovascular regeneration therapies include human mesenchymal stem cells (hMSCs) and pluripotent stem cell derived cardiomyocytes (hPS-CM) each with their own unique method for improving cardiac function post-infarct. However, a limiting factor to cell therapies is that the methods currently used to deliver cells to the myocardium, including intramyocardial injection (considered the gold standard), suffer from low retention rates. To promote localization of delivered cells to the infarct and increase retention rates, our lab has developed a fibrin biological suture that can deliver human mesenchymal stem cells (hMSCs) with an efficiency of 64% compared to just 11% with intramyocardial injection in the normal rat heart. In this dissertation we sought to examine the functionality of hMSC and hPS-CM seeded sutures and their impact on cardiovascular regeneration applications. We began by delivering hMSC seeded fibrin sutures to an infarcted rat heart and found that the sutures are an effective method to deliver cells to the infarcted myocardium and demonstrated a trend towards improved regional mechanical function in the infarct region over infarct alone. Next, we transitioned to using hPS-CM and developed methods to seed the sutures, as well as a method to measure hPS-CM contractility with high spatial and temporal resolution, while concurrently capturing calcium transients. This technique allowed us to examine the contractile behavior in terms of contractile strain and conduction velocity of hPS-CM seeded on fibrin microthreads over 21 days in culture. We found that the fibrin microthread is a suitable scaffold for hPS-CM attachment and contraction and that extended culture promotes cell alignment along the length of the suture as well as improvements in contractile function in terms of increases in contractile strain and conduction velocity. Finally, we delivered the hPS-CM seeded microthreads to an uninjured rat heart and found a delivery efficiency of 67%. Overall, we further demonstrated the technology of the fibrin suture to deliver cells to an infarct as well as the ability to support the attachment, contraction and delivery of hPS-CM to cardiac tissue. "

L'ablation par radiofréquence constitue un des traitements des tachycardies ventriculaires, en association avec les drogues anti-arythmiques et l’implantation d'un défibrillateur. L’objectif principal de cette thèse est de mieux comprendre le substrat arythmogène non seulement à l’aide d'imagerie cardiaque (IRM et scanner) de haute résolution et de cartographie de haute densité, en utilisant des cathéters multipolaires. Cela nous permettra d'analyser la relation structure-fonction. Nous avons étudié cette relation sur différents types de substrats (ICM, NICM, DAVD, et myocardites). Nous avons ainsi prouvé la supériorité de la cartographie de haute densité obtenue à partir de cathéters multipolaires, comparativement aux données recueillies par l’imagerie, dans l’identification de la cicatrice arythmogène et la détection des LAVA. La deuxième partie de cette thèse concerne l’étude du substrat arythmogène épicardique. Nous avons ainsi décrit la technique de cartographie par voie percutanée antérieure, puis démontré l'efficacité des procédures uniquement avec abord épicardique. La segmentation du nerf phrénique et des artères coronaires ont permis de diminuer le taux de complications théoriquement liés à cet abord. Nous avons poursuivi ce travail avec l’analyse des sites d'intérêt de l'ablation des TV: les LAVA. Après une description de la stratégie d’élimination des LAVA, nous avons tenté de trouver des prédicteurs permettant de localiser les sites de LAVA, à partir des données d'imagerie. Quand l'imagerie montre une cicatrice intraseptale ou intramurale, les LAVA ne peuvent pas être enregistrés avec la cartographie et des alternative techniques d'ablation sont nécessaires comme une ablation bipolaire, l'alcoolisation intra coronaire et l'ablation avec l'aiguille irriguée. Le dernier chapitre est une revue sur le futur de l'imagerie, de la cartographie et de l’ablation des tachycardies ventriculaires. Une meilleure compréhension du substrat arythmogène pourrait améliorer l'efficacité et la sécurité des ablations de tachycardie ventriculaire. / Radiofrequency (RF) catheter ablation is an effective treatment strategy for scar-related ventricular tachycardia (VT), resistant to anti-arrhythmic drugs and intracardiac defibrillator (ICD) placement. The goal of this thesis was to better understand and characterize the arrhythmogenic VT substrate in different cardiomyopathic processes: ischaemic cardiomyopathy (ICM), non-ischaemic cardiomyopathy (NICM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and myocarditis. For this purpose, we combined high resolution imaging including different modalities and high resolution electrical mapping to better understand the structure-function relationship. We focused on multiple different aspects of VT ablation as outlined below. The first part of this thesis focuses on the role of multipolar mapping catheters and imaging to analyze their structural and functional relationship. We demonstrated superiority of high density mapping with multipolar mapping on conventional mapping in detection of scar, channels, local abnormal ventricular activity (LAVA) and sensitivity for near field signals. The second part of this thesis focuses on ablation of epicardial VT substrate. We demonstrated the efficacy and safety of epicardial only procedures in a highly selected population. We used imaging to have access to the exact anatomy of the heart, to image the substrate but also to increase the safety of ablation procedures by imaging the phrenic nerve and the coronary artery system. The third part of this thesis focuses on analysis of the mapping and ablation of potential targets for scar-related VT ablation. Within this context, we identified predictors of interesting ablation (LAVA) sites based on preprocedural imaging. We also analyzed the role of alternative strategies such as bipolar ablation, ethanol ablation and irrigated needle ablation to ablate intramural and intraseptal substrate, 18 often resistant ablation targets. Overall, we demonstrate that novel imaging, mapping and ablation techniques potentially improve the outcome of VT ablation.

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