Abstract Background: Implantable cardioverter-defibrillator (ICD) surgery in patients with implanted left ventricular assist devices (LVAD) is associated with an increased risk of bleeding complications because of the need to ensure that these patients are adequately anticoagulated. Our study aimed to evaluate the safety of our new strategy of uninterrupted oral anticoagulation compared to heparin-bridging during the surgical interval. Methods: Between January 2009 and January 2020, 116 patients with LVAD underwent ICD surgery. Since January 2015, 60 patients were operated under continued sufficient oral anticoagulation with a vitamin k antagonist (VKA group). Fifty-six patients underwent a heparin-bridging regimen (heparin group). Demographics, perioperative data, complications, and mortality were analyzed. Results: Bleeding complications attributable to the surgical intervention occurred more often (19.6% vs. 10.0%, p = 0.142) and at a higher rate of re-exploratory surgery (14.3% vs. 5.0%, p = 0.088) in the heparin group without reaching statistical significance. Moreover, the heparin group patients' postoperative total length of stay was 10 days longer (17.8 ± 23.8 days vs. 8.3 ± 9.5 days, p = 0.007). There were no procedure-related deaths, no thromboembolic events, and no LVAD-related thrombosis. Conclusion: Our strategy of uninterrupted oral anticoagulation is safe and results in a reduction by more than half the number of days in hospital without an increase in adverse events.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui vise à rétablir le synchronisme de contraction du ventricule gauche chez les patients souffrant d’insuffisance cardiaque. Aujourd’hui encore, plus de 30% de ces patients ne répondent pas au traitement de resynchronisation. Afin de mieux comprendre les effets de la CRT sur la fonction cardiaque, un resynchronisateur biventriculaire a été implanté chez des chiens sains et des chiens atteints d’insuffisance cardiaque. Les fonctions ventriculaires gauche et droite ont été étudiées selon différents modes de resynchronisation. Les résultats de cette étude confirment premièrement que la durée du complexe QRS n’est pas un marqueur approprié dans l’optimisation de la CRT. Les résultats démontrent également qu’une optimisation individualisée de la CRT est nécessaire afin de maximiser l’effet de la thérapie sur le ventricule gauche et que la modulation du délai de resynchronisation a un impact significatif sur la fonction ventriculaire droite. Plus précisément, la fonction systolique du ventricule droit est optimale lors d’une activation précoce de l’électrode gauche. / Cardiac resynchronization therapy (CRT) was introduced to reestablish the synchronism in left ventricular of heart failure patients. At the present time, more than 30% of these patients do not respond to the resynchronization treatments. In order to better understand the effect of CRT on the cardiac function, a biventricular pacemaker was implanted in healthy dogs and in dogs with induced heart failure. Results from this study show that using the QRS duration in order to optimize CRT is not recommended. In addition, they confirm that an individualized optimization of the CRT is necessary to maximize the effect of the therapy on the left ventricle and that the modulation of the resynchronization delay has a significant impact on the right ventricular function. More precisely, right ventricular systolic function is optimal with an early activation of the left electrode.

Introdução: A terapia de ressincronização cardíaca (TRC) é um tratamento recomendado pelas principais diretrizes mundiais para pacientes com insuficiência cardíaca congestiva (ICC), disfunção ventricular esquerda (FE <= 35%), com tratamento otimizado e distúrbio da condução intraventricular, principalmente pelo ramo esquerdo. Entretanto, 30%-40% dos pacientes selecionados não respondem ao tratamento. As razões desse insucesso não são completamente conhecidas. Existe, portanto, necessidade de desenvolvimento de índices multifatoriais para melhor selecionar e acompanhar a evolução e o prognóstico destes pacientes. Objetivo: Elaborar modelos preditores de risco de óbito cardíaco ou transplante (Tx), em diferentes fases da TRC. Métodos e Casuística: Estudo observacional, prospectivo e analítico, com inclusão de 116 pacientes, entre 01/2008 a 03/2013, sendo 69,8% do sexo masculino, com CF III (68,1%) e IV ambulatorial (31,9%), com BRE em 71,55% e com idade de 64,89 ± 11,18 anos e fração de ejeção (FE) de 29%. Avaliações foram feitas no período pré-implante (tempo 1), 6-12 meses (tempo 2) e 18-24 meses (tempo 3) e correlacionadas com a mortalidade cardíaca/Tx no final do seguimento. Foram estudadas variáveis clínicas, eletrocardiográficas e ecocardiográficas e realizadas análises de regressão de Cox e regressão logística, com a construção da curva ROC. As curvas de sobrevidas foram realizadas pelo método de Kaplan-Meier e comparadas pelo log-rank. Modelos e escores foram elaborados pelas pontuações do \"hazard ratio\", utilizado como variável independente no modelo de regressão logística. Resultados: Ocorreram 29 (25%) óbitos/Tx durante o seguimento de 34,09 ± 17,9 meses. A mortalidade cardíaca/Tx foi de 16,3 % (19 pacientes). Seis pacientes foram transplantados durante o tempo do estudo. No período préimplante (tempo 1), a presença de disfunção de ventrículo direito (VD), FE < 25% e o uso de altas doses de diuréticos (dois ou mais comprimidos de furosemida) mostraram-se com valor independente, com aumento de risco de óbito cardíaco/Tx de 3,9; 4,8 e 5,9 vezes, respectivamente. No tempo 2 (1° ano), as variáveis disfunção de VD, altas doses de diuréticos e internações por ICC foram as variáveis significativas, com aumento de risco 3,5; 5,3 e 12,5 respectivamente. No tempo 3 (2° ano), as variáveis disfunção de VD e classe funcional III/IV foram significativas no modelo multivariado de Cox, com aumento de risco de 12,1 e 7,7. As acurácias dos modelos foram 84,6%; 93% e 90,5%, respectivamente. Conclusão: Os modelos preditores de óbito cardíaco desenvolvidos a partir de variáveis clínicas e ecocardiográficas, obtidas em diferentes fases da TRC, mostraram boa acurácia e podem ajudar na seleção, seguimento, definição de resposta e aconselhamento destes pacientes / Introduction: Cardiac resynchronization therapy (CRT) is indicated for patients with congestive heart failure (CHF), ejection fraction (EF) <= 35%, and bundle branch block. However, 30%-40% do not respond to CRT. Therefore, there is a need to develop multifactorial indexes to better select and follow these patients. Objective: This work aims to develop predictive models for the risk of cardiac death or transplantation (Tx) at different stages of CRT. Methods: We performed a prospective observational study of 116 patients, 69.8% males, functional class (FC) III (68.1%) and IV (31.9%), LBBB in 71.55%, age 64.89 ± 11.18 years. We studied clinical, electrocardiographic, and echocardiographic variables and performed Cox and logistic regression with ROC and Kaplan- Meier curves. Results: The cardiac mortality was 16.3% (19 patients) in the 34.09 ± 17.9 follow-up months. Pre-implantation, the right ventricular dysfunction (RVD), EF <25%, and the use of high doses of diuretics (HDD) increased risk of cardiac death or Tx of 3.9, 4.8, and 5.9 fold, respectively, and in the first year, the variables RVD, HDD, and hospitalizations for CHF increased risk of death of 3.5, 5.3, and 12.5, respectively. In the 2nd year, the variables RVD and FC III / IV (NYHA) were significant in the multivariate Cox model. The accuracies of the models were 84.6%, 93%, and 90.5%, respectively. Conclusions: Cardiac death predictive models were developed in different stages of CRT, and were based on the analysis of simple clinical and echocardiographic variables. The models showed good accuracy and can help in the selection and follow-up of these patients

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui vise à rétablir le synchronisme de contraction du ventricule gauche chez les patients souffrant d’insuffisance cardiaque. Aujourd’hui encore, plus de 30% de ces patients ne répondent pas au traitement de resynchronisation. Afin de mieux comprendre les effets de la CRT sur la fonction cardiaque, un resynchronisateur biventriculaire a été implanté chez des chiens sains et des chiens atteints d’insuffisance cardiaque. Les fonctions ventriculaires gauche et droite ont été étudiées selon différents modes de resynchronisation. Les résultats de cette étude confirment premièrement que la durée du complexe QRS n’est pas un marqueur approprié dans l’optimisation de la CRT. Les résultats démontrent également qu’une optimisation individualisée de la CRT est nécessaire afin de maximiser l’effet de la thérapie sur le ventricule gauche et que la modulation du délai de resynchronisation a un impact significatif sur la fonction ventriculaire droite. Plus précisément, la fonction systolique du ventricule droit est optimale lors d’une activation précoce de l’électrode gauche. / Cardiac resynchronization therapy (CRT) was introduced to reestablish the synchronism in left ventricular of heart failure patients. At the present time, more than 30% of these patients do not respond to the resynchronization treatments. In order to better understand the effect of CRT on the cardiac function, a biventricular pacemaker was implanted in healthy dogs and in dogs with induced heart failure. Results from this study show that using the QRS duration in order to optimize CRT is not recommended. In addition, they confirm that an individualized optimization of the CRT is necessary to maximize the effect of the therapy on the left ventricle and that the modulation of the resynchronization delay has a significant impact on the right ventricular function. More precisely, right ventricular systolic function is optimal with an early activation of the left electrode.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui diminue la mortalité et améliore la qualité de vie des patients atteints d’insuffisance cardiaque et présentant un dyssynchronisme de la contraction ventriculaire gauche. Malgré le succès de cette thérapie, plus de 30% des patients ne présentent pas l’amélioration désirée. Plusieurs études portant sur le synchronisme électrique ou mécanique de la contraction ont été effectuées mais peu d’entres elles se sont attardées sur le couplage électromécanique à l'échelle macroscopique. Ce projet a comme objectif d’observer le comportement électromécanique des ventricules canins en présence d’un resynchronisateur cardiaque. Un logiciel a été développé pour permettre l’analyse des informations provenant de la cartographie endocardique sans contact et de la ventriculographie isotopique tomographique chez 12 sujets canins insuffisants. Pour observer la réponse mécanique suite à l’activation électrique, nous avons premièrement recalé les surfaces issues des 2 modalités. Ensuite, nous avons défini les limites du cycle cardiaque, analysé les signaux électriques et les courbes de déplacement de la paroi endocardique. Le début de la contraction est défini par un déplacement radial de 10% vers le centre du ventricule. Les résultats démontrent que la durée d’activation du ventricule gauche et la largeur du QRS augmentent en présence d’une stimulation externe et que les délais électromécaniques sont indépendants dans les modes de stimulation étudiés (sinusal, LVbasal, RVapex ou BIV) avec une moyenne de 84,56±7,19 ms. Finalement, nous avons noté que la stimulation basolatérale procure une fonction cardiaque optimale malgré une durée prolongée du QRS. / Cardiac Resynchronization Therapy (CRT) is known to decrease mortality rate and improve the quality of life for patients suffering from heart failure with left ventricular contraction dyssynchrony. However, it has been shown that 30% of patients do not respond to this therapy. Many studies have investigated the electrical or mechanical synchronism of contraction but few have studied the activation contraction coupling on a macroscopic level. The objective of this study is to observe the left ventricle’s electromechanical behaviour under biventricular stimulation. A software has been developed to analyse the data coming from non-contact mapping and blood pool SPECT for 12 dogs with heart failure. In order to observe the mechanical response following an electrical activation, we have registered 3D surfaces generated by the 2 modalities. Afterward, we defined the cardiac cycle limits, and we analyzed electrical signals as well as endocardial wall displacement curves where the onset of contraction was defined as a 10% inward radial displacement. Results show that both duration of left ventricular activation and QRS increase with pacing and that electromechanical delays are independent of stimulation mode (mean value 84,56 ± 7,19 ms). Finally, we observed that basolateral stimulation shows the best improvement for left ventricular function while presenting a long QRS duration.

Synchronous contraction and relaxation of the myocardium is required to optimize cardiac function. Regional timing of contraction and relaxation is dyssynchronous in many patients with heart failure. Cardiac resynchronization therapy (CRT) is a highly successful treatment for dyssynchronous heart failure. Patients are currently selected for CRT using surface electrocardiogram QRS duration as a measure of dyssynchrony. However, up to 30% of patients selected for CRT show no improvement. This poor response rate may in part be explained by the poor correlation between mechanical dyssynchrony and QRS duration. Thus, better methods to quantify mechanical dyssynchrony in the heart may improve the poor CRT response rate. The overall goal of this project was to develop better methods to diagnose dyssynchrony in the left ventricle (LV). We developed two new methods with different approaches. The first method improved upon existing tissue-Doppler based echocardiographic diagnosis of dyssynchrony by utilizing a cross-correlation (XC) function to quantify dyssynchrony during post-processing as opposed to the quantitatively simplistic time-to-peak analysis that is currently utilized. The second method utilized standard cine cardiac magnetic resonance (CMR) images to quantify the dyssynchrony in the flow of blood within the LV, which may represent a more direct, physiologically relevant measure of dyssynchrony. Specific aim 1 demonstrated that the new XC delay parameters can be quantified accurately with a stationary region of interest and therefore require significantly less post-processing time to calculate compared to the time-to-peak dyssynchrony parameters. Specific aim 2 showed that XC delays are superior to existing time-to-peak dyssynchrony parameters at discriminating patients with LV dyssynchrony from those with normal function. The time-to-peak parameters showed dyssynchrony in approximately half of the normal, healthy volunteers while the XC delay parameters had nearly perfect diagnostic accuracy. The results of specific aim 3 showed that XC delays could diagnose acute, pacing-induced dyssynchrony in young, healthy children with 79% accuracy while the time-to-peak parameters showed accuracies of 71%, 57% and 57%. Specific aim 4 showed that CMR-based quantification of LV internal flow can be used to discriminate patients with dyssynchronous heart failure from normal controls with 95% accuracy.

Introdução: A terapia de ressincronização cardíaca (TRC) é um tratamento recomendado pelas principais diretrizes mundiais para pacientes com insuficiência cardíaca congestiva (ICC), disfunção ventricular esquerda (FE <= 35%), com tratamento otimizado e distúrbio da condução intraventricular, principalmente pelo ramo esquerdo. Entretanto, 30%-40% dos pacientes selecionados não respondem ao tratamento. As razões desse insucesso não são completamente conhecidas. Existe, portanto, necessidade de desenvolvimento de índices multifatoriais para melhor selecionar e acompanhar a evolução e o prognóstico destes pacientes. Objetivo: Elaborar modelos preditores de risco de óbito cardíaco ou transplante (Tx), em diferentes fases da TRC. Métodos e Casuística: Estudo observacional, prospectivo e analítico, com inclusão de 116 pacientes, entre 01/2008 a 03/2013, sendo 69,8% do sexo masculino, com CF III (68,1%) e IV ambulatorial (31,9%), com BRE em 71,55% e com idade de 64,89 ± 11,18 anos e fração de ejeção (FE) de 29%. Avaliações foram feitas no período pré-implante (tempo 1), 6-12 meses (tempo 2) e 18-24 meses (tempo 3) e correlacionadas com a mortalidade cardíaca/Tx no final do seguimento. Foram estudadas variáveis clínicas, eletrocardiográficas e ecocardiográficas e realizadas análises de regressão de Cox e regressão logística, com a construção da curva ROC. As curvas de sobrevidas foram realizadas pelo método de Kaplan-Meier e comparadas pelo log-rank. Modelos e escores foram elaborados pelas pontuações do \"hazard ratio\", utilizado como variável independente no modelo de regressão logística. Resultados: Ocorreram 29 (25%) óbitos/Tx durante o seguimento de 34,09 ± 17,9 meses. A mortalidade cardíaca/Tx foi de 16,3 % (19 pacientes). Seis pacientes foram transplantados durante o tempo do estudo. No período préimplante (tempo 1), a presença de disfunção de ventrículo direito (VD), FE < 25% e o uso de altas doses de diuréticos (dois ou mais comprimidos de furosemida) mostraram-se com valor independente, com aumento de risco de óbito cardíaco/Tx de 3,9; 4,8 e 5,9 vezes, respectivamente. No tempo 2 (1° ano), as variáveis disfunção de VD, altas doses de diuréticos e internações por ICC foram as variáveis significativas, com aumento de risco 3,5; 5,3 e 12,5 respectivamente. No tempo 3 (2° ano), as variáveis disfunção de VD e classe funcional III/IV foram significativas no modelo multivariado de Cox, com aumento de risco de 12,1 e 7,7. As acurácias dos modelos foram 84,6%; 93% e 90,5%, respectivamente. Conclusão: Os modelos preditores de óbito cardíaco desenvolvidos a partir de variáveis clínicas e ecocardiográficas, obtidas em diferentes fases da TRC, mostraram boa acurácia e podem ajudar na seleção, seguimento, definição de resposta e aconselhamento destes pacientes / Introduction: Cardiac resynchronization therapy (CRT) is indicated for patients with congestive heart failure (CHF), ejection fraction (EF) <= 35%, and bundle branch block. However, 30%-40% do not respond to CRT. Therefore, there is a need to develop multifactorial indexes to better select and follow these patients. Objective: This work aims to develop predictive models for the risk of cardiac death or transplantation (Tx) at different stages of CRT. Methods: We performed a prospective observational study of 116 patients, 69.8% males, functional class (FC) III (68.1%) and IV (31.9%), LBBB in 71.55%, age 64.89 ± 11.18 years. We studied clinical, electrocardiographic, and echocardiographic variables and performed Cox and logistic regression with ROC and Kaplan- Meier curves. Results: The cardiac mortality was 16.3% (19 patients) in the 34.09 ± 17.9 follow-up months. Pre-implantation, the right ventricular dysfunction (RVD), EF <25%, and the use of high doses of diuretics (HDD) increased risk of cardiac death or Tx of 3.9, 4.8, and 5.9 fold, respectively, and in the first year, the variables RVD, HDD, and hospitalizations for CHF increased risk of death of 3.5, 5.3, and 12.5, respectively. In the 2nd year, the variables RVD and FC III / IV (NYHA) were significant in the multivariate Cox model. The accuracies of the models were 84.6%, 93%, and 90.5%, respectively. Conclusions: Cardiac death predictive models were developed in different stages of CRT, and were based on the analysis of simple clinical and echocardiographic variables. The models showed good accuracy and can help in the selection and follow-up of these patients

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui diminue la mortalité et améliore la qualité de vie des patients atteints d’insuffisance cardiaque et présentant un dyssynchronisme de la contraction ventriculaire gauche. Malgré le succès de cette thérapie, plus de 30% des patients ne présentent pas l’amélioration désirée. Plusieurs études portant sur le synchronisme électrique ou mécanique de la contraction ont été effectuées mais peu d’entres elles se sont attardées sur le couplage électromécanique à l'échelle macroscopique. Ce projet a comme objectif d’observer le comportement électromécanique des ventricules canins en présence d’un resynchronisateur cardiaque. Un logiciel a été développé pour permettre l’analyse des informations provenant de la cartographie endocardique sans contact et de la ventriculographie isotopique tomographique chez 12 sujets canins insuffisants. Pour observer la réponse mécanique suite à l’activation électrique, nous avons premièrement recalé les surfaces issues des 2 modalités. Ensuite, nous avons défini les limites du cycle cardiaque, analysé les signaux électriques et les courbes de déplacement de la paroi endocardique. Le début de la contraction est défini par un déplacement radial de 10% vers le centre du ventricule. Les résultats démontrent que la durée d’activation du ventricule gauche et la largeur du QRS augmentent en présence d’une stimulation externe et que les délais électromécaniques sont indépendants dans les modes de stimulation étudiés (sinusal, LVbasal, RVapex ou BIV) avec une moyenne de 84,56±7,19 ms. Finalement, nous avons noté que la stimulation basolatérale procure une fonction cardiaque optimale malgré une durée prolongée du QRS. / Cardiac Resynchronization Therapy (CRT) is known to decrease mortality rate and improve the quality of life for patients suffering from heart failure with left ventricular contraction dyssynchrony. However, it has been shown that 30% of patients do not respond to this therapy. Many studies have investigated the electrical or mechanical synchronism of contraction but few have studied the activation contraction coupling on a macroscopic level. The objective of this study is to observe the left ventricle’s electromechanical behaviour under biventricular stimulation. A software has been developed to analyse the data coming from non-contact mapping and blood pool SPECT for 12 dogs with heart failure. In order to observe the mechanical response following an electrical activation, we have registered 3D surfaces generated by the 2 modalities. Afterward, we defined the cardiac cycle limits, and we analyzed electrical signals as well as endocardial wall displacement curves where the onset of contraction was defined as a 10% inward radial displacement. Results show that both duration of left ventricular activation and QRS increase with pacing and that electromechanical delays are independent of stimulation mode (mean value 84,56 ± 7,19 ms). Finally, we observed that basolateral stimulation shows the best improvement for left ventricular function while presenting a long QRS duration.

L'évaluation de l'asynchronisme mécanique ventriculaire sous stress a soulevé une attention importante en tant que facteur prédictif de la réponse au traitement de resynchronisation cardiaque (CRT). De plus, il semble exister une relation significative entre le devenir du patient et la présence d’asynchronisme au repos. Plusieurs méthodes échocardiographiques peuvent être utilisées pour évaluer l’asynchronisme. Cependant, parmi toutes les différentes méthodologies ou index existant dans ce domaine, aucun critère ne fait l’unanimité. Cette thèse étudie l'importance des techniques d'imagerie nucléaire dans le cadre de l’évaluation de l’asynchronisme cardiaque induit par le stress en utilisant trois différents modèles canins expérimentaux. Le premier chapitre vise à examiner les effets du stress sur le synchronisme de la contraction du ventricule gauche (VG) en utilisant l'imagerie synchronisée de perfusion myocardique dans une cohorte canine normale. Le stress a été induit par différents niveaux d’infusion de dobutamine sur six sujets sains. Les paramètres hémodynamiques et l’asynchronisme ont été évalués par des mesures de pressions ventriculaires. L'analyse de phase sur l’imagerie s’est effectuée en utilisant un logiciel commercialement disponible (QGS) et un logiciel interne (MHI4MPI), basée sur le déplacement et l’épaississement des parois ventriculaires. L’augmentation de la concentration de dobutamine a démontré une amélioration de la capacité fonctionnelle et une réduction de l’asynchronisme ventriculaire. L’analyse de l’asynchronisme calculée à partir de l’épaississement de la paroi semble plus robuste et plus sensible que l’utilisation du déplacement des parois. (Salimian et. al., J Nucl Cardiol., 2014) Le second chapitre étudie les différents paramètres d’asynchronisme au repos et à différents niveaux de stress dans un modèle de cardiomyopathie dilatée et à QRS étroit. Ce modèle a été créé sur dix chiens par tachycardie via stimulation de l'apex du ventricule droit pendant 3-4 semaines, permettant d’atteindre une fraction d'éjection cible de 35% ou moins. Le stress a ensuite été induit par une perfusion de dobutamine jusqu'à un maximum de 20 μg/kg/min. Les données hémodynamiques et l’asynchronisme ont été analysés par des mesures de pression ventriculaire et l’analyse de l’imagerie dynamique du compartiment sanguin. L’importante variabilité individuelle des sujets inclus dans notre cohorte empêche toute conclusion définitive sur la mesure de l’asynchronisme interventriculaire. Cependant, les différents niveaux de stress, même dans des intervalles rapprochés, ont démontré un effet significatif sur les paramètres hémodynamiques et l’asynchronisme. (Salimian et. al., J Nucl Cardiol., 2015) La troisième section vise à déterminer si l’estimation du mode de stimulation optimal effectuée au repos demeure le choix optimal lorsque le niveau d’activité cardiaque s’intensifie pour des sujets avec bloc auriculo-ventriculaire (AV) et fonction ventriculaire normale. Cinq chiens ont été soumis à une ablation du nœud AV et des sondes de stimulation ont été insérées dans l'oreillette droite pour la détection, l’apex du ventricule droit (VD) et une veine postérolatérale du VG pour la stimulation. Cinq modes de stimulation ont été utilisés : LV pur, biventriculaire (BiV) avec pré-activation de 20 ms du LV (LVRV20), BiV pur, BiV avec pré-activation de 20 ms du VD (RVLV20), VD pur. Des niveaux jusqu’à 20 μg/kg/min de dobutamine ont été atteints. Le stress a modifié l’étendue de l’asynchronisme de base et ce, pour tous les modes de stimulation. De plus, les effets physiologiques intrinsèques du stress permettent une évaluation plus précise de l’asynchronisme ventriculaire, diminuant la variabilité inter-sujet. Le mode de stimulation LVRV20 semble le mode optimal dans ce modèle, supportant l’utilisation de la stimulation bi-ventriculaire. / Assessment of ventricular mechanical dyssynchrony (MD) under stress has attracted a large amount of attention as a stronger predictor of response to cardiac resynchronization therapy (CRT) and as a parameter whose variation bears a greater relationship to clinical outcomes than resting-MD either in CRT candidates or another subset of patients. Several echocardiographic methods can be used to assess stress-MD. However, no standardized approach is currently used to explore stress-induced variations in inter- and intraventricular MD. This dissertation studies the importance of nuclear imaging techniques in assessing stress-induced MD variations by providing three different experimental canine models. The first chapter sought to examine the impacts of stress on the left ventricular (LV) synchrony with phase analysis of gated SPECT myocardial perfusion imaging (GMPS) within a normal canine cohort. Stress was induced by different levels of dobutamine infusion in six healthy subjects. Hemodynamic and LV MD parameters were assessed by LV pressure measurements and phase analysis of GMPS using commercially available QGS software and in-house MHI4MPI software with thickening- and displacement-based methodology. The increase of dobutamine level was shown to be in accordance with the improvement of LV functional capacity and reduction of MD parameters. MD analysis based on wall thickening was more robust and sensitive than the global wall displacement. (Salimian et. al., J Nucl Cardiol., 2014) The second chapter investigated the range of difference in inter- and intraventricular MD parameters from rest to various levels of stress in a dilated cardiomyopathy (DCM) and narrow QRS complex model. Ten large dogs were submitted to tachycardia-induced DCM by pacing the right ventricular apex for 3-4 weeks to reach a target ejection fraction of 35% or less. Stress was then induced by infusion of dobutamine up to a maximum of 20 μg/kg/min. Hemodynamic and MD data were analyzed by LV pressure measurements and gated-blood pool SPECT (GBPS) imaging. Individual differences in the magnitude and pattern of change in the various levels of stress precluded any definitive conclusion about interventricular MD. However, different levels of stress, even in close intervals, showed a significant positive impact on hemodynamic and intraventricular MD parameters. (Salimian et. al., J Nucl Cardiol., 2015) The third chapter sought to examine if the optimal pacing mode at rest could be the best one during the maximum stress level in terms of MD parameters in subjects with an atrioventricular (AV) block and normal function. Five dogs were submitted to AV node ablation and pacing leads were placed in the right atrium for sensing, in right ventricular (RV) apex, and in posterolateral LV vein for pacing in five modes of LV, biventricular (BiV) with 20 ms of LV pre-activation (LVRV20), BiV, BiV with 20 ms of RV pre-activation (RVLV20) and RV pacing. Stress was induced by dobutamine infusion up to a maximum of 20 μg/kg/min. Data analyses were the same as chapter one. Dobutamine stress changed the extent of resting-LV MD at all pacing modes. Intrinsic physiologic effects of stress resulted in more accurate MD assessment with lesser variability in subjects who underwent pacing. LVRV20 was the preferred site of stimulation in this model rather than single-site pacing.

Cette thèse porte sur la caractérisation cardiaque, qui représente un enjeu méthodologique et clinique important, à la fois pour améliorer le diagnostic des pathologies et optimiser les moyens de traitement. Des méthodes de recalage et de fusion de données sont proposées pour amener dans un même référentiel des images IRM, scanner, échographiques et électro-anatomiques et ainsi décrire le cœur suivant des caractéristiques anatomiques, électriques, mécaniques et tissulaires. Les méthodes proposées pour recaler des données multimodales reposent sur deux processus principaux : l'alignement temporel et le recalage spatial. Les dimensions temporelles des images considérées sont mises en synchronisées par une méthode de déformation temporelle dynamique adaptative. Celle-ci permet de compenser les modifications temporelles non-linéaires entre les différentes acquisitions. Pour le recalage spatial, des méthodes iconiques ont été développées pour corriger les artefacts de mouvements dans les séquences ciné-IRM, pour recaler les séquences ciné-IRM avec les séquences d'IRM de rehaussement tardif et pour recaler les ciné-IRM avec les images scanner. D'autre part, une méthode basée contours, développée dans un précédent travail, a été améliorée pour prendre en compte des acquisitions échographiques multi-vues. Ces méthodes ont été évaluées sur données réelles pour sélectionner les métriques les plus adaptées et pour quantifier les performances des approches iconiques et pour estimer la précision du recalage entre échographies et ciné-IRM. Ces méthodes sont appliquées à la caractérisation de cardiomyopathies hypertrophiques (CMH) et d'asynchronismes cardiaques. Pour la CMH, l'objectif était de mieux interpréter les données échographiques par la fusion de l'information de fibrose issue de l'IRM de rehaussement tardif avec l'information mécanique issue de l'échographie de speckle tracking. Cette analyse a permis d'évaluer le strain régional en tant qu'indicateur de la présence locale de fibrose. Concernant l'asynchronisme cardiaque, nous avons établi une description du couplage électromécanique local du ventricule gauche par la fusion de données échographiques, électro-anatomiques, scanner et, dans les cas appropriés, d'IRM de rehaussement tardif. Cette étude de faisabilité ouvre des perspectives pour l'utilisation de nouveaux descripteurs pour la sélection des sites de stimulation optimaux pour la thérapie de resynchronisation cardiaque. / This work concerns cardiac characterization, a major methodological and clinical issue, both to improve disease diagnostic and to optimize its treatment. Multisensor registration and fusion methods are proposed to bring into a common referential data from cardiac magnetic resonance (CMRI), dynamic cardiac X-ray computed tomography (CT), speckle tracking echocardiography (STE) and electro-anatomical mappings of the inner left ventricular chamber (EAM). These data is used to describe the heart by its anatomy, electrical and mechanical function, and the state of the myocardial tissue. The methods proposed to register the multimodal datasets rely on two main processes: temporal registration and spatial registration. The temporal dimensions of input data (images) are warped with an adaptive dynamic time warping (ADTW) method. This method allowed to handle the nonlinear temporal relationship between the different acquisitions. Concerning the spatial registration, iconic methods were developed, on the one hand, to correct for motion artifacts in cine acquisition, to register cine-CMRI and late gadolinium CMRI (LGE-CMRI), and to register cine-CMRI with dynamic CT. On the other hand, a contour-based method developed in a previous work was enhanced to account for multiview STE acquisitions. These methods were evaluated on real data in terms of the best metrics to use and of the accuracy of the iconic methods, and to assess the STE to cine-CMRI registration. The fusion of these multisensor data enabled to get insights about the diseased heart in the context of hypertrophic cardiomyopathy (HCM) and cardiac asynchronism. For HCM, we aimed to improve the understanding of STE by fusing fibrosis from LGE-CMRI with strain from multiview 2D STE. This analysis allowed to assess the significance of regional STE strain as a surrogate of the presence of regional myocardial fibrosis. Concerning cardiac asynchronism, we aimed to describe the intra-segment electro-mechanical coupling of the left ventricle using fused data from STE, EAM, CT and, if relevant, from LGE-CMRI. This feasibility study provided new elements to select the optimal sites for LV stimulation.