Quantification of cardiac left ventricular (LV) motion from medical images provides a non-invasive method for diagnosing cardiovascular disease (CVD). The proposed study continues our group\'s line of research in quantification of LV motion by applying optical flow (OF) techniques to quantify LV motion in gated Rubidium Chloride-82Rb (82Rb) and Fluorodeoxyglucose-18F (FDG) PET image sequences. The following challenges arise from this work: (i) the motion vector field (MVF) should be made as accurate as possible to maximise sensitivity and specificity; (ii) the MVF is large and composed of 3D vectors in 3D space, making visual extraction of information for medical diagnosis dffcult by human observers. Approaches to improve the accuracy of motion quantification were developed. While the volume of interest is the region of the MVF corresponding to the LV myocardium, non-zero values of motion exist outside this volume due to artefacts in the motion detection method or from neighbouring structures, such as the right ventricle. Improvements in accuracy can be obtained by segmenting the LV and setting the MVF to zero outside the LV. The LV myocardium was automatically segmented in short-axis slices using the Hough circle transform to provide an initialisation to the distance regularised level set evolution algorithm. Our segmentation method attained Dice similarity measure of 93.43% when tested over 395 FDG slices, compared with manual segmentation. Strategies for improving OF performance at motion boundaries were investigated using spatially varying averaging filters, applied to synthetic image sequences. Results showed improvements in motion quantification accuracy using these methods. Kinetic Energy Index (KEf), an indicator of cardiac motility, was used to assess 63 individuals with normal and altered/low cardiac function from a 82Rb PET image database. Sensitivity and specificity tests were performed to evaluate the potential of KEf as a classifier of cardiac function, using LV ejection fraction as gold standard. A receiver operating characteristics curve was constructed, which provided an area under the curve of 0.906. Analysis of LV motion can be simplified by visualisation of directional motion field components, namely radial, rotational (or circumferential) and linear, obtained through automated decomposition. The Discrete Helmholtz Hodge Decomposition (DHHD) was used to generate these components in an automated manner, with a validation performed using synthetic cardiac motion fields from the Extended Cardiac Torso phantom. Finally, the DHHD was applied to OF fields from gated FDG images, allowing an analysis of directional components from an individual with normal cardiac function and a patient with low function and a pacemaker fitted. Motion field quantification from PET images allows the development of new indicators to diagnose CVDs. The ability of these motility indicators depends on the accuracy of the quantification of movement, which in turn can be determined by characteristics of the input images, such as noise. Motion analysis provides a promising and unprecedented approach to the diagnosis of CVDs. / A quantificação do movimento cardíaco do ventrículo esquerdo (VE) a partir de imagens médicas fornece um método não invasivo para o diagnóstico de doenças cardiovasculares (DCV). O estudo aqui proposto continua na mesma linha de pesquisa do nosso grupo sobre quantificação do movimento do VE por meio de técnicas de fluxo óptico (FO), aplicando estes métodos para quantificar o movimento do VE em sequências de imagens associadas às substâncias de cloreto de rubídio-82Rb (82Rb) e fluorodeoxiglucose-18F (FDG) PET. Com a extração dos campos vetoriais surgiram os seguintes desafios: (i) o campo vetorial de movimento (motion vector field, MVF) deve ser feito da forma mais precisa possível para maximizar a sensibilidade e especificidade; (ii) o MVF é extenso e composto de vetores 3D no espaço 3D, dificultando a análise visual de informações por observadores humanos para o diagnóstico médico. Foram desenvolvidas abordagens para melhorar a precisão da quantificação de movimento, considerando que o volume de interesse seja a região do MVF correspondente ao miocárdio do VE, em que valores de movimento não nulos existem fora deste volume devido aos artefatos do método de detecção de movimento ou de estruturas vizinhas, como o ventrículo direito. As melhorias na precisão foram obtidas segmentando o VE e ajustando os valores de MVF para zero fora do VE. O miocárdio VE foi segmentado automaticamente em fatias de eixo curto usando a Transformada de Hough na detecção de círculos para fornecer uma inicialização ao algoritmo de curvas de nível, um tipo de modelo deformável. A segmentação automática do VE atingiu 93,43% de medida de similaridade Dice, quando foi testado em 395 fatias de eixo menor de FDG, comparado com a segmentação manual. Estratégias para melhorar o desempenho do algoritmo OF nas bordas de movimento foram investigadas usando spatially varying averaging filters, aplicados em seqüências de imagens sintéticas. Os resultados mostraram melhorias na precisão de quantificação de movimento utilizando estes métodos. O Índice de Energia Cinética (KEf), um indicador de motilidade cardíaca, foi utilizado para avaliar 63 sujeitos com função cardíaca normal e alterada / baixa de uma base de dados de imagens PET de 82Rb. Foram realizados testes de sensibilidade e especificidade para avaliar o potencial de KEf para classificar a função cardíaca, utilizando a fração de ejeção do VE como padrão ouro. Foi construída uma curva ROC, que proporcionou uma área sob a curva de 0,906. A análise do movimento do VE pode ser simplificada pela visualização de componentes de campo de movimento direcional, ou seja, radial, rotacional (ou circunferencial) e linear, obtidos por decomposição automatizada. A decomposição discreta de Helmholtz Hodge (DHHD) foi utilizada para gerar estes componentes de forma automatizada, com uma validação utilizando campos de movimento cardíaco sintéticos a partir do conjunto Extended Cardiac Torso Phantom. Finalmente, o método DHHD foi aplicado a campos de FO, criado a partir de imagens FDG, permitindo uma análise de componentes direcionais de um indivíduo com função cardíaca normal e um paciente com baixa função e utilizando um marca-passo. A quantificação do campo de movimento a partir de imagens PET possibilita o desenvolvimento de novos indicadores para diagnosticar DCVs. A capacidade destes indicadores de motilidade depende na precisão da quantificação de movimento que, por sua vez, pode ser determinado por características das imagens de entrada como ruído. A análise de movimento fornece um promissor e sem precedente método para o diagnóstico de DCVs.

Quantification of cardiac left ventricular (LV) motion from medical images provides a non-invasive method for diagnosing cardiovascular disease (CVD). The proposed study continues our group\'s line of research in quantification of LV motion by applying optical flow (OF) techniques to quantify LV motion in gated Rubidium Chloride-82Rb (82Rb) and Fluorodeoxyglucose-18F (FDG) PET image sequences. The following challenges arise from this work: (i) the motion vector field (MVF) should be made as accurate as possible to maximise sensitivity and specificity; (ii) the MVF is large and composed of 3D vectors in 3D space, making visual extraction of information for medical diagnosis dffcult by human observers. Approaches to improve the accuracy of motion quantification were developed. While the volume of interest is the region of the MVF corresponding to the LV myocardium, non-zero values of motion exist outside this volume due to artefacts in the motion detection method or from neighbouring structures, such as the right ventricle. Improvements in accuracy can be obtained by segmenting the LV and setting the MVF to zero outside the LV. The LV myocardium was automatically segmented in short-axis slices using the Hough circle transform to provide an initialisation to the distance regularised level set evolution algorithm. Our segmentation method attained Dice similarity measure of 93.43% when tested over 395 FDG slices, compared with manual segmentation. Strategies for improving OF performance at motion boundaries were investigated using spatially varying averaging filters, applied to synthetic image sequences. Results showed improvements in motion quantification accuracy using these methods. Kinetic Energy Index (KEf), an indicator of cardiac motility, was used to assess 63 individuals with normal and altered/low cardiac function from a 82Rb PET image database. Sensitivity and specificity tests were performed to evaluate the potential of KEf as a classifier of cardiac function, using LV ejection fraction as gold standard. A receiver operating characteristics curve was constructed, which provided an area under the curve of 0.906. Analysis of LV motion can be simplified by visualisation of directional motion field components, namely radial, rotational (or circumferential) and linear, obtained through automated decomposition. The Discrete Helmholtz Hodge Decomposition (DHHD) was used to generate these components in an automated manner, with a validation performed using synthetic cardiac motion fields from the Extended Cardiac Torso phantom. Finally, the DHHD was applied to OF fields from gated FDG images, allowing an analysis of directional components from an individual with normal cardiac function and a patient with low function and a pacemaker fitted. Motion field quantification from PET images allows the development of new indicators to diagnose CVDs. The ability of these motility indicators depends on the accuracy of the quantification of movement, which in turn can be determined by characteristics of the input images, such as noise. Motion analysis provides a promising and unprecedented approach to the diagnosis of CVDs. / A quantificação do movimento cardíaco do ventrículo esquerdo (VE) a partir de imagens médicas fornece um método não invasivo para o diagnóstico de doenças cardiovasculares (DCV). O estudo aqui proposto continua na mesma linha de pesquisa do nosso grupo sobre quantificação do movimento do VE por meio de técnicas de fluxo óptico (FO), aplicando estes métodos para quantificar o movimento do VE em sequências de imagens associadas às substâncias de cloreto de rubídio-82Rb (82Rb) e fluorodeoxiglucose-18F (FDG) PET. Com a extração dos campos vetoriais surgiram os seguintes desafios: (i) o campo vetorial de movimento (motion vector field, MVF) deve ser feito da forma mais precisa possível para maximizar a sensibilidade e especificidade; (ii) o MVF é extenso e composto de vetores 3D no espaço 3D, dificultando a análise visual de informações por observadores humanos para o diagnóstico médico. Foram desenvolvidas abordagens para melhorar a precisão da quantificação de movimento, considerando que o volume de interesse seja a região do MVF correspondente ao miocárdio do VE, em que valores de movimento não nulos existem fora deste volume devido aos artefatos do método de detecção de movimento ou de estruturas vizinhas, como o ventrículo direito. As melhorias na precisão foram obtidas segmentando o VE e ajustando os valores de MVF para zero fora do VE. O miocárdio VE foi segmentado automaticamente em fatias de eixo curto usando a Transformada de Hough na detecção de círculos para fornecer uma inicialização ao algoritmo de curvas de nível, um tipo de modelo deformável. A segmentação automática do VE atingiu 93,43% de medida de similaridade Dice, quando foi testado em 395 fatias de eixo menor de FDG, comparado com a segmentação manual. Estratégias para melhorar o desempenho do algoritmo OF nas bordas de movimento foram investigadas usando spatially varying averaging filters, aplicados em seqüências de imagens sintéticas. Os resultados mostraram melhorias na precisão de quantificação de movimento utilizando estes métodos. O Índice de Energia Cinética (KEf), um indicador de motilidade cardíaca, foi utilizado para avaliar 63 sujeitos com função cardíaca normal e alterada / baixa de uma base de dados de imagens PET de 82Rb. Foram realizados testes de sensibilidade e especificidade para avaliar o potencial de KEf para classificar a função cardíaca, utilizando a fração de ejeção do VE como padrão ouro. Foi construída uma curva ROC, que proporcionou uma área sob a curva de 0,906. A análise do movimento do VE pode ser simplificada pela visualização de componentes de campo de movimento direcional, ou seja, radial, rotacional (ou circunferencial) e linear, obtidos por decomposição automatizada. A decomposição discreta de Helmholtz Hodge (DHHD) foi utilizada para gerar estes componentes de forma automatizada, com uma validação utilizando campos de movimento cardíaco sintéticos a partir do conjunto Extended Cardiac Torso Phantom. Finalmente, o método DHHD foi aplicado a campos de FO, criado a partir de imagens FDG, permitindo uma análise de componentes direcionais de um indivíduo com função cardíaca normal e um paciente com baixa função e utilizando um marca-passo. A quantificação do campo de movimento a partir de imagens PET possibilita o desenvolvimento de novos indicadores para diagnosticar DCVs. A capacidade destes indicadores de motilidade depende na precisão da quantificação de movimento que, por sua vez, pode ser determinado por características das imagens de entrada como ruído. A análise de movimento fornece um promissor e sem precedente método para o diagnóstico de DCVs.

Cardiac rehabilitation (CR) exercise training, which traditionally involves the prescription of moderate intensity continuous exercise, can slow the progression of heart disease and improve cardiorespiratory fitness (CRF). Cardiac function is typically investigated using calculations of ejection fraction (EF) from echocardiography, yet EF measures do not provide information about the unique twisting motion of the heart. Novel measures of cardiac function, such as LV twist, myocardial performance index (MPI) and global longitudinal strain (GLS), may provide additional information about changes in LV mechanics associated with exercise training for individuals with coronary artery disease (CAD). The aims of this study were to investigate the changes in cardiac function, using both standard and novel measures, at baseline (0 weeks; T1), post-initial training (4 weeks; T2), and post-training (12 weeks; T3) in response to either stair climbing-based high intensity interval training (STAIR) or traditional moderate intensity continuous training (TRAD). We recruited 16 individuals with CAD (61±7years; 1W) and randomized them into TRAD and STAIR groups (n=8/group). Standard (CRF and EF), and novel (LV twist, MPI, GLS), measures of cardiovascular function were assessed at all three timepoints. CRF improved in both groups, after 4 and 12 weeks (STAIR: T1:22.1±4.2, T2:24.7±4.9, T3:25.4±5.2 and TRAD: T1:22.8±2.5, T2:25.2±4.9, T3:26.0±5.0 mL/kg/min; P<0.005) of CR exercise. We observed an increase in apical rotation (P=0.01) and LV twist (P=0.03), but no changes in either traditional (EF P=0.15), or novel (MPI P=0.19; GLS P=0.81) measures of cardiac function over time, in either group. It is possible that the relatively short training period (12 weeks) was not sufficient to result in significant changes in cardiac function, despite improvements in CRF. Future research should assess both standard and novel indices of cardiac function over longer exercise training periods to determine the ideal indices for tracking changes over time with interventions in this population. / Thesis / Master of Science (MSc) / Cardiac rehabilitation exercise is an important part of recovery after a heart attack, and it has been shown to improve heart function measured using standard ultrasound assessments. Studies have suggested that novel measures of heart function may be more sensitive in comparison to these standard ultrasound measures, yet these novel measures have not been examined in individuals completing stair-climbing based high intensity cardiac rehabilitation exercise training. This work examined the changes in both novel and standard ultrasound measures of heart function after either stair climbing-based high intensity interval training or traditional moderate intensity exercise training in individuals who have heart disease. While this study found that both stair climbing based high intensity interval training and traditional cardiac rehabilitation both resulted in increases in cardiorespiratory fitness after 12 weeks of training, no changes were observed in any of the standard measures of heart function. Supporting the concept that novel measures of heart function might be more sensitive, as some training associated changes were observed in the novel measures of heart function.

Introdução: A doença falciforme (DF) é a afecção hematológica hereditária de maior prevalência no mundo, sendo que a anemia falciforme (AF) é a forma mais grave com elevada morbidade e mortalidade. Alterações cardíacas são reconhecidamente associadas à AF, como aumento cavitário, hipertensão arterial pulmonar e disfunção diastólica do ventrículo esquerdo. No entanto, ainda não existe consenso quanto à função sistólica ventricular nesses pacientes. O objetivo deste estudo foi o de investigar a função ventricular de pacientes com anemia falciforme utilizando o strain e o twist ventricular obtidos pelo speckle tracking bidimensional, e reconhecer os indivíduos sob maior risco cardiovascular, em que a instituição precoce de tratamento específico poderá beneficiar essa população. Métodos: Foram recrutados 40 pacientes com anemia falciforme (23,5 ± 9,3 anos; 24 homens) e 40 controles saudáveis pareados por sexo e idade, submetidos à entrevista estruturada, ecocardiograma transtorácico, cintilografia pulmonar ventilação perfusão e coleta de amostras de sangue. Todos os indivíduos foram submetidos à avaliação ecocardiográfica convencional padrão e subsequente avaliação offline do strain sistólico biventricular e estudo rotacional do ventrículo esquerdo utilizando speckle-tracking ecocardiográfico. Resultados: Os pacientes com AF apresentaram volume do VE indexado, massa do VE indexado, pressão arterial pulmonar e E/E\' médio superiores aos controles. As medidas de FE do VE, excursão sistólica do plano da tricúspide (TAPSE), Strain Global do VE (longitudinal, circunferencial, radial) e Strain Global do VD (longitudinal) não evidenciaram diferenças entre os grupos. Twist VE se mostrou reduzido em comparação aos controles (7,4 ± 1,2? vs 10,7 ± 1,8? , P <0,0001 ) e Tempo de pico de rotação apical prolongado (366,7 ± 26,1ms vs 344,6 ± 11,7ms , P <0,0001 ). Algumas variáveis se mostraram fortemente relacionadas ao twist VE, como índice de gravidade clínico (Rho= - 0,97, Z value= - 6,05, P < 0,0001), relação E/E\' médio (r = 0,94, F valor= 156.9, p<0,0001), IVDFVE (índice do volume diastólico final do ventrículo esquerdo)(r = 0,81 e p<0,0001) e pressão sistólica arterial pulmonar (r = 0,72 e p<0,0001). Conclusões: Os resultados deste trabalho indicam que o twist ventricular esquerdo derivado do speckle tracking bidimensional encontra-se alterado em pacientes com anemia falciforme e função sistólica ventricular preservada, avaliada pela metodologia convencional, e existe forte correlação entre o twist ventricular esquerdo e o índice clínico de gravidade, relação E/E\', índice do volume diastólico final do ventrículo esquerdo e pressão sistólica arterial pulmonar. / Background: Sickle cell disease (SCD) is the most prevalent hematological condition in the world, with sickle cell anemia (SCA) being its most serious form, displaying a high level of morbidity and mortality. Cardiac changes are known to be associated with SCA, including an increase in cardiac chamber size, pulmonary hypertension and left ventricle diastolic dysfunction. However, there is still no consensus regarding the ventricular systolic function in these patients. The purpose of this study is to investigate the ventricular function of patients with sickle cell anemia utilizing the strain and ventricular twist, obtained by two-dimensional speckle tracking, as well as to identify individuals with higher cardiovascular risk, in which early application of specific treatment could benefit this group of people. Methods: 40 patients were recruited with sickle cell anemia (ages 23.5 ± 9.3 years; 24 males) and 40 healthy control individuals paired by gender and age, submitted to structured interviews, transthoracic echocardiogram, pulmonary scintigraphy and collection of blood samples. All individuals were submitted to a standard echocardiographic evaluation and subsequent off line evaluation of the biventricular systolic strain and rotational study of the left ventricle using echocardiographic speckle-tracking. Results: Patients with SCA presented LV volume indices, LV mass Indices, pulmonary arterial pressure and E/ E\' ratios statistically higher than the control individuals. Measurements of Ejection Fraction (EF) of the left ventricle, tricuspid annular plane systolic excursion (TAPSE), Overall LV Strain (Longitudinal, Circumferential, and Radial) and Overall RV Strain (Longitudinal) did not present differences between the groups. LV twist was significantly lower in relation to the control group (7,4 ± 1,2? vs 10,7 ± 1,8? , P <0,0001 ) and prolonged time to peak apical rotation (366.7 ± 26.1ms vs 344.6 ± 11.7ms , P <0.0001 ). In addition, some variables showed themselves to be strongly related to LV twist such as the clinical severity index ( Rho= - 0.97, Z value= - 6.05, P < 0.0001), E/E\' Ratio (r = 0.94, F value=156.9 e p<0.0001) ), left ventricle end diastolic volume index (LVEDV index) (r = 0,81, p<0,0001) and pulmonary systolic arterial pressure (r = 0.72 e p<0.0001). Conclusions: The results of this study indicate that the left ventricular twist derived from two-dimensional speckle tracking is altered in patients with sickle cell anemia and a preserved ventricular systolic function, evaluated using conventional methodology and that there is a strong correlation between left ventricular twist and the clinical severity index, E/E\' ratio, left ventricle end diastolic volume index and the pulmonary systolic arterial pressure.

Introdução: A doença falciforme (DF) é a afecção hematológica hereditária de maior prevalência no mundo, sendo que a anemia falciforme (AF) é a forma mais grave com elevada morbidade e mortalidade. Alterações cardíacas são reconhecidamente associadas à AF, como aumento cavitário, hipertensão arterial pulmonar e disfunção diastólica do ventrículo esquerdo. No entanto, ainda não existe consenso quanto à função sistólica ventricular nesses pacientes. O objetivo deste estudo foi o de investigar a função ventricular de pacientes com anemia falciforme utilizando o strain e o twist ventricular obtidos pelo speckle tracking bidimensional, e reconhecer os indivíduos sob maior risco cardiovascular, em que a instituição precoce de tratamento específico poderá beneficiar essa população. Métodos: Foram recrutados 40 pacientes com anemia falciforme (23,5 ± 9,3 anos; 24 homens) e 40 controles saudáveis pareados por sexo e idade, submetidos à entrevista estruturada, ecocardiograma transtorácico, cintilografia pulmonar ventilação perfusão e coleta de amostras de sangue. Todos os indivíduos foram submetidos à avaliação ecocardiográfica convencional padrão e subsequente avaliação offline do strain sistólico biventricular e estudo rotacional do ventrículo esquerdo utilizando speckle-tracking ecocardiográfico. Resultados: Os pacientes com AF apresentaram volume do VE indexado, massa do VE indexado, pressão arterial pulmonar e E/E\' médio superiores aos controles. As medidas de FE do VE, excursão sistólica do plano da tricúspide (TAPSE), Strain Global do VE (longitudinal, circunferencial, radial) e Strain Global do VD (longitudinal) não evidenciaram diferenças entre os grupos. Twist VE se mostrou reduzido em comparação aos controles (7,4 ± 1,2? vs 10,7 ± 1,8? , P <0,0001 ) e Tempo de pico de rotação apical prolongado (366,7 ± 26,1ms vs 344,6 ± 11,7ms , P <0,0001 ). Algumas variáveis se mostraram fortemente relacionadas ao twist VE, como índice de gravidade clínico (Rho= - 0,97, Z value= - 6,05, P < 0,0001), relação E/E\' médio (r = 0,94, F valor= 156.9, p<0,0001), IVDFVE (índice do volume diastólico final do ventrículo esquerdo)(r = 0,81 e p<0,0001) e pressão sistólica arterial pulmonar (r = 0,72 e p<0,0001). Conclusões: Os resultados deste trabalho indicam que o twist ventricular esquerdo derivado do speckle tracking bidimensional encontra-se alterado em pacientes com anemia falciforme e função sistólica ventricular preservada, avaliada pela metodologia convencional, e existe forte correlação entre o twist ventricular esquerdo e o índice clínico de gravidade, relação E/E\', índice do volume diastólico final do ventrículo esquerdo e pressão sistólica arterial pulmonar. / Background: Sickle cell disease (SCD) is the most prevalent hematological condition in the world, with sickle cell anemia (SCA) being its most serious form, displaying a high level of morbidity and mortality. Cardiac changes are known to be associated with SCA, including an increase in cardiac chamber size, pulmonary hypertension and left ventricle diastolic dysfunction. However, there is still no consensus regarding the ventricular systolic function in these patients. The purpose of this study is to investigate the ventricular function of patients with sickle cell anemia utilizing the strain and ventricular twist, obtained by two-dimensional speckle tracking, as well as to identify individuals with higher cardiovascular risk, in which early application of specific treatment could benefit this group of people. Methods: 40 patients were recruited with sickle cell anemia (ages 23.5 ± 9.3 years; 24 males) and 40 healthy control individuals paired by gender and age, submitted to structured interviews, transthoracic echocardiogram, pulmonary scintigraphy and collection of blood samples. All individuals were submitted to a standard echocardiographic evaluation and subsequent off line evaluation of the biventricular systolic strain and rotational study of the left ventricle using echocardiographic speckle-tracking. Results: Patients with SCA presented LV volume indices, LV mass Indices, pulmonary arterial pressure and E/ E\' ratios statistically higher than the control individuals. Measurements of Ejection Fraction (EF) of the left ventricle, tricuspid annular plane systolic excursion (TAPSE), Overall LV Strain (Longitudinal, Circumferential, and Radial) and Overall RV Strain (Longitudinal) did not present differences between the groups. LV twist was significantly lower in relation to the control group (7,4 ± 1,2? vs 10,7 ± 1,8? , P <0,0001 ) and prolonged time to peak apical rotation (366.7 ± 26.1ms vs 344.6 ± 11.7ms , P <0.0001 ). In addition, some variables showed themselves to be strongly related to LV twist such as the clinical severity index ( Rho= - 0.97, Z value= - 6.05, P < 0.0001), E/E\' Ratio (r = 0.94, F value=156.9 e p<0.0001) ), left ventricle end diastolic volume index (LVEDV index) (r = 0,81, p<0,0001) and pulmonary systolic arterial pressure (r = 0.72 e p<0.0001). Conclusions: The results of this study indicate that the left ventricular twist derived from two-dimensional speckle tracking is altered in patients with sickle cell anemia and a preserved ventricular systolic function, evaluated using conventional methodology and that there is a strong correlation between left ventricular twist and the clinical severity index, E/E\' ratio, left ventricle end diastolic volume index and the pulmonary systolic arterial pressure.

L’hypertension artérielle chronique induit une hypertrophie ventriculaire gauche, à l’origine d’une dysfonction diastolique caractérisée par des troubles de la relaxation, de la compliance et du remplissage ventriculaires gauches, le tout aggravé par toute augmentation de la fréquence cardiaque. Le couplage contraction-relaxation physiologique implique, en cas de préservation dans ce contexte d’hypertrophie ventriculaire gauche, que cette dysfonction diastolique s’accompagne d’une dysfonction systolique. Ainsi, ce travail de thèse s’est attaché (1) à caractériser la fonction ventriculaire gauche et le couplage contraction-relaxation à l’aide de la mesure de la torsion et la détorsion, (2) à étudier les mécanismes cellulaires impliqués dans le couplage contraction-relaxation et (3) à explorer les effets d’une stratégie thérapeutique visant à réduire la fréquence cardiaque sur la torsion et la détorsion du ventricule gauche dans un modèle d’hypertension artérielle chronique et d’hypertrophie ventriculaire induites chez le porc chroniquement instrumenté par la perfusion continue d’angiotensine II pendant 28 jours. A J28, la torsion et la détorsion étaient diminuées et la détorsion également retardée au sein du cycle cardiaque, alors que la fraction d’éjection ventriculaire gauche était préservée. Le couplage contraction-relaxation était préservé, tant au niveau du ventricule gauche qu’à l’échelon cardiomyocytaire, suggérant que toute dysfonction diastolique devrait faire rechercher une dysfonction systolique. A J28, ces anomalies fonctionnelles s’accompagnaient d’une diminution de l’expression de la SERCA2a et de sa protéine régulatrice le phospholamban. Des anomalies du récepteur de la ryanodine de type 2 étaient aussi observées avec son hyperphosphorylation et la dissociation de sa protéine régulatrice calstabine 2, à l’origine de fuites calciques systoliques et diastoliques. Ce dernier pourrait ainsi jouer un rôle clé dans la préservation du couplage contraction-relaxation et représenter l’intégrateur entre les anomalies ventriculaire gauche systolique et diastolique observées. Enfin, la réduction pharmacologique de la fréquence cardiaque à J28 par l’ivabradine, un inhibiteur sélectif des canaux If, permettait d’améliorer, en partie par des effets fréquence-indépendants dont les mécanismes cellulaires restent à élucider, tant les anomalies ventriculaire gauche diastolique que systolique, avec une amélioration des temps de contraction et de relaxation isovolumiques, de la torsion et de la détorsion ainsi que du remplissage du ventricule gauche. En l’absence d’hypertrophie ventriculaire gauche, la réduction de la fréquence cardiaque à des valeurs inférieures à 60 batt/min s’accompagnait d’un effet délétère fréquence-dépendant, à l’origine d’une altération isolée de la fonction diastolique caractérisée par une diminution de la détorsion du ventricule gauche et une augmentation de la pression télédiastolique ventriculaire gauche. La caractérisation de la fonction ventriculaire gauche et l’étude du couplage contraction-relaxation par la mesure de la torsion et de la détorsion en cas de décompensation cardiaque restent à déterminer. / Chronic hypertension induces left ventricular (LV) hypertrophy, resulting in abnormalities in LV relaxation, passive stiffness and filling. The higher the heart rate, the more pronounced the LV diastolic dysfunction. Moreover, in the normal heart, there is a tight coupling between LV contraction and relaxation, implying that in case of preserved contraction-relaxation coupling during LV hypertrophy, there is no diastolic dysfunction without systolic dysfunction. Thus, the three main objectives of this thesis were to investigate 1) the LV function and contraction-relaxation coupling with LV twist and untwist, which represent LV myocardial deformation during systole and diastole, 2) the cellular mechanisms of the LV contraction-relaxation coupling and 3) the effects effects of heart rate reduction on LV twist and untwist in the context of chronic hypertension and LV hypertrophy. All experiments were conducted in a pig model of chronic hypertension and LV hypertrophy induced by four weeks of continuous angiotensin II infusion. Chronic angiotensin II infusion decreased LV twist and untwist but also delayed LV untwist in the cardiac cycle, whereas the LV ejection fraction was preserved. The contraction-relaxation coupling was preserved as illustrated by the strong relationship between LV twist and untwist. The contraction-relaxation coupling was also preserved at the level of cardiomyocytes. This implies that LV hypertrophy is associated with concomitant LV diastolic and systolic dysfunction despite preserved LV ejection fraction. Thus, LV diastolic dysfunction is always accompanied by LV systolic dysfunction, i.e., the discovery of LV diastolic dysfunction with preserved ejection fraction might imply the track of LV systolic dysfunction. At the cellular level, LV systolic and diastolic dysfunctions were associated to aberrant calcium handling with a remodelling of the type 2 ryanodine receptor calcium release channel (RyR2), i.e., PKA-hyperphosphorylation and depletion of calstabin 2 (FKBP12.6). RyR2 were leaky and hypersensitive to cytosolic calcium, during both the contraction and the relaxation phases. Since both LV systolic and diastolic dysfunctions were associated to leaky and hypersensitive RyR2 channels, it might suggest considering RyR2 as an integrator contributing to control contraction-relaxation coupling during chronic hypertension and LV hypertrophy. Finally, we investigated the effects of heart rate reduction induced by ivabradine, an If-channel blocker, which does not modify atrioventricular or LV conduction and is devoid of any intrinsic negative inotropic or lusitropic effects. In the context of chronic hypertension and LV hypertrophy, ivabradine improved both LV systolic and diastolic functions, as attested by the improvement in contraction and relaxation times, LV twist and untwist as well as LV filling. Heart-rate independent effects of ivabradine, i.e., pleiotropic effects, participate to its beneficial effect. However, the cellular mechanisms of these beneficial effects of ivabradine were not elucidated and require further investigations. In normal heart, when heart rate was reduced to a low level (approximately <60 beats/min) with ivabradine, LV twist was not affected but LV diastolic function was altered as suggested by decreased LV untwist parameters and increased LV end-diastolic pressure. Investigation of contraction-relaxation coupling during decompensation from stable LV hypertrophy remains a goal to achieve.