A disfunção ventricular esquerda (VE) é o principal determinante de mau prognóstico nos pacientes com bloqueio atrioventricular completo congênito (BAVTC) e marcapasso (MP). A dissincronia mecânica do VE pode desempenhar um papel importante no desenvolvimento da disfunção ventricular. Como o uso do MP é um fator de risco para dissincronia, nosso(s) objetivo(s) foram: (1) avaliar a dissincronia do VE pelo ecocardiograma tridimensional (3D) em tempo real e comparar com os parâmetros de dissincronia pelo Doppler tecidual ; (2) verificar a possível correlação entre o local do estímulo e o segmento ativado tardiamente; (3) correlacionar o tempo de marcapasso e a presença de dissincronia e remodelamento ventricular. Avaliamos 50 pacientes com BAVTC e MP através do ecocardiograma bidimensional (2D), Doppler tecidual e ecocardiograma tridimensional. Dados clínicos e anteriores ao implante do MP foram revistos pelos prontuários. Houve 12 (23,5%) pacientes com dissincronia pelo 3D e 14 (28%) pelo Doppler tecidual. Em 16 (32%) e 20 (40%) havia disfunção ventricular esquerda pelos 2D e 3D respectivamente. O remodelamento ventricular ocorreu em 50% dos pacientes. Houve uma excelente correlação entre o Doppler tecidual e o 3D para diagnóstico de dissincronia (kappa = 0,735, p <0,001). A fração de ejeção do VE (FEVE) correlacionou-se negativamente com a dissincronia pelo eco 3D (r= -0,58, p = 0,000001). A duração do ciclo cardíaco medida pelo intervalo RR teve também uma significante correlação negativa com o índice de dissincronia pelo 3D (r=-0,74, p=0,0011). O remodelamento do VE pelo Eco 3D (índices de esfericidade e conicidade) teve uma boa correlação com a disfunção do VE (p = 0,005 e 0,003 respectivamente). O tempo de marcapasso, a idade do implante e o local do eletrodo não se correlacionaram com a dissincronia. Comparando os pacientes com BAVTC e MP menores que 18 anos com um grupo controle de crianças normais, houve uma significante diferença em relação aos volumes do VE, índices de dissincronia, esfericidade e conicidade. Em conclusão, neste estudo transversal de pacientes com BAVTC e uso crônico de MP, o ecocardiograma tridimensional teve uma excelente correlação com o Doppler tecidual no diagnóstico de dissincronia mecânica. A posição do eletrodo não foi preditora do segmento ativado tardiamente. O tempo de MP não se correlacionou com a presença de dissincronia e disfunção do VE. Houve uma boa correlação entre a dissincronia, remodelamento e disfunção do VE / The left ventricle (LV) dysfunction is the major reason for poor outcome in patients with congenital complete atrioventricular block (CCAVB) and pacemaker (PM). The LV mechanical dyssynchrony may play a significant role in the development of LV dysfunction in this population. As the long-term pacing is a potential risk factor for dyssynchrony, we sought to: (1) evaluate by real time three-dimensional echocardiography (RT3DE) the LV dyssynchrony and compare with Tissue Doppler (TDI) parameters; (2) verify the potential correlation between the electrode location and the latest segment activated; (3) correlate the time of pacing and LV dyssynchrony and LV remodeling. Two-dimensional (2D), TDI and RT3DE were performed in 50 patients with CCAVB and PM (mean age of 21,4 years DP 13,4). Clinical data were reviewed. Twelve (23,5%) had LV dyssynchrony by RT3DE and 14 (28%) by Tissue Doppler criteria. Sixteen (32%) and 20 (40%) had LV dysfunction by 2D and 3D, respectively. LV remodeling occurred in 50% of patients. There was an excellent correlation between RT3DE and TDI (Kappa = 0,735; p <0,001). The LV ejection fraction (LVEF) had a significant negative correlation with the dyssynchrony index by 3D (r = -0,58, p = 0,000001). The duration of the cardiac cycle measured by RR interval had a significant negative correlation with the LV dyssynchrony index by 3D (r = - 0,74, p = 0,0011). LV remodeling demonstrated by the sphericity and conic indexes had a good correlation with the presence of LV dysfunction (p = 0,005 and 0,003 respectively). The pacing time, the age at pacemaker implantation and the location of the electrode did not correlate with LV dyssynchrony. Patients bellow 18 years of age were significantly different in terms of LV dyssynchrony indexes, LV remodeling and LV volumes when compared with a control group with similar age and body surface area. In conclusion, in a cohort study of patients with CCAVB and long-term pacing, the RT3DE had an excellent correlation with TDI to evaluate LV dyssynchrony. The pacing site was not a predictor of the latest segment activation. The pacing time did not correlate with LV dyssynchrony and dysfunction. There was a correlation between the LV dyssynchrony and the presence of remodeling and dysfunction

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.

Made available in DSpace on 2016-08-19T18:16:04Z (GMT). No. of bitstreams: 1 Dissertacao Gilvan.pdf: 1264814 bytes, checksum: 315e543380c1d084e9507ab66fbf221f (MD5) Previous issue date: 2012-06-18 / Background: A specific acromegaly-related cardiomyopathy has been described in the literature, largely in Caucasians, which is independent of other risk factors, mainly hypertension. Objective: The aim of this study was to assess the cardiac changes in an extensively admixed acromegalic population and also the relevance of the aetiopathogenic factors involved, such as disease activity and hypertension. Methods: In a cross-sectional design, 37 acromegalic patients (20 brown, 14 blacks and 3 whites) and 74 controls matched by age, gender and hypertension were evaluated. Cardiac morphology and function were addressed using echocardiography parameters. Results: The mean age of patients was 46.9 ± 12.8 years, with 67.6% being female and 43.2% hypertensive. The prevalence of left ventricular hypertrophy (LVH) between acromegalics was 56.8% versus 10.8% in the controls (p< 0.001). About 86% of patients with LVH had active disease (p = 0.023). Logistic regression revealed that disease activity presented a stronger association (OR = 5.925; CI = 1.085 32.351; p = 0.040) with LVH than hypertension (OR = 3.237; CI = 0.702 14.924; p = 0.132). Most acromegalics (51.4%) presented with diastolic dysfunction that directly correlated with age and with blood pressure levels and did not correlate with the percentage of upper limit of the normal range of IGF-I (% ULNR-IGF-I). Systolic function was not affected. When black acromegalics were compared to brown ones, no statistically significant differences were observed. Conclusion: In conclusion, chronically hyperactive somatotropic axis remains as an independent and determining factor in the development of LVH, as it is more associated with this condition than hypertension in a largely admixed population with a high prevalence of blacks. / Introdução: Uma miocardiopatia específica da acromegalia vem sendo descrita na literatura, principalmente em caucasianos e que é independente de outros fatores de risco, sobretudo, da Hipertensão Arterial Sistêmica (HAS). Objetivo: avaliar as alterações cardíacas em uma população acromegálica altamente miscigenada, assim como a importância dos fatores etiopatogênicos envolvidos, a saber: atividade da doença e HAS. Metodologia: Em um estudo transversal, 37 pacientes acromegálicos (20 pardos, 14 negros e 3 brancos) e 74 indivíduos do grupo controle pareados por faixa etária, sexo e presença de HAS foram avaliados. A morfologia e a função cardíacas foram avaliadas usando parâmetros ecocardiográficos. Resultados: a média de idade dos pacientes foi de 46.9 ± 12.8 anos, com 67.6% de mulheres e 43.2% de hipertensos. A prevalência de hipertrofia de ventrículo esquerdo (HVE) entre acromegálicos foi de 56.8% versus 10.8% no grupo-controle (p< 0.001). Cerca de 86% dos pacientes com HVE apresentaram doença ativa (p = 0.023). A análise por regressão logística demonstrou que a atividade da doença apresentou uma associação mais forte (OR = 5.925; CI = 1.085 32.351; p = 0.040) com HVE que HAS (OR = 3.237; CI = 0.702 14.924; p = 0.132). A maioria dos acromegálicos (51.4%) apresentou disfunção diastólica que se correlacionou diretamente com a idade e com os níveis de pressão arterial e não demonstrou correlação com a percentagem do limite superior da variação do normal de IGF-I (% LSN-IGF-I). Não houve alteração da função sistólica. Diferenças estatisticamente significantes não foram observadas quando os acromegálicos negros foram comparados aos pardos. Conclusão: A hiperatividade do eixo somatotrófico permanece como um fator determinante e independente para o desenvolvimento de HVE, visto que é mais associado com esta condição que HAS, em uma população de acromegálicos de ampla diversidade étnica e com alta prevalência de negros.

Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.

Purpose: Patients living with advanced heart failure experience dyspnea, fatigue, poor quality of life, depression and cognitive impairment which may threaten their ability to provide informed consent to undergo heart transplant (HTx) or mechanical support (LVAD). Using qualitative and quantitative methods, we asked how patients with advanced heart failure make decisions regarding HTx and LVAD. The variables chosen to reflect the elements of consent included quality of life and symptom severity (voluntariness), depression and cognitive impairment (capacity) and treatment preferences (decision-making). Methods: 76 patients enrolled in the quantitative arm completed the Minnesota Living with Heart Failure Questionnaire; Visual Analog scales for dyspnea, fatigue and overall health; Beck Depression Inventory; Montreal Cognitive Assessment; Standard Gamble and Time Tradeoff. Qualitative methods were used to discover concepts, relationships and decision-making processes described by 17 of the 76 patients considering HTx and LVAD. Results: Patients reported poor quality of life and high symptom severity scores which compelled them to consider surgery as a way to relieve unpleasant symptoms and improve quality of life. Although 30% of patients had evidence of depression and/or cognitive impairment, no patient was deemed incapable of decision-making. Patients were willing to take considerable risk (35%) and trade considerable time (4months) to improve their health. While heart failure-related concepts were important to the decision, entrustment emerged as the meaningful process for decision-making. Conclusions: Patients who participated in this study were capable of decision-making and understood the risks associated with the surgery. Voluntariness was diminished by disease but not absent, and decisions were free of coercion. These results suggest the entrustment model of decision-making is the dominant process for patients considering high-risk surgical procedures and meets criteria for informed consent. Understanding the process of decision-making will help clinicians support and enable treatment decisions made by patients living with advanced heart failure.

The objective of this thesis is to evaluate the use of Doppler echocardiography markers ofglobal dyssynchrony [total isovolumic time (t-IVT)] in the following 6 studies: 1) Its prognostic role in predicting cardiac events in patients undergoing CABG surgery,compared with conventional global systolic and diastolic measurements. 2) Its additional value in predicting six minute walk test (6-MWT) in patients with leftventricular (LV) ejection fraction (EF) &lt;45%. 3) Its prognostic value in comparison with other clinical, biochemical and echocardiographicvariables in patients with chronic systolic heart failure (HF). 4) The relationship between 6-MWT and cardiac function measurements in a consecutivegroup of patients, irrespective of EF and to identify predictors of exercise capacity. 5) To investigate the effect of age on LV t-IVT and Tei index compared with conventionalsystolic and diastolic parameters. 6) To assess potential additional value of markers of global LV dyssynchrony in predictingcardiac resynchronization therapy (CRT) response in HF patients. Study I Methods: This study included 74 patients before routine CABG who were followed up for18±12 months. Results: At follow-up, 29 patients were hospitalized for a cardiac event or died. LV-ESD wasgreater (P=0.003), fractional shortening (FS) lower (p&lt;0.001), E:A ratio and Tei index higher(all P&lt;0.001), and t-IVT longer (P&lt;0.001) in patients with events. Low FS [0.66 (0.50–0.87),P&lt;0.001], high E:A ratio [l4.13 (1.17–14.60), P=0.028], large LV-ESD [0.19 (0.05–0.84),P=0.029], and long t-IVT [1.37 (1.02–1.84), P=0.035] predicted events and deaths. Conclusion: Despite satisfactory surgical revascularization, long t-IVT and systolicdysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABGcardiac events. Study II Methods: We studied 77 patients (60±12 year, and 33.3% females) with stable HF using 6-MWT.iii Results: E’ wave (r=0.61, p&lt;0.001), E/e’ ratio (r=-0.49, p&lt;0.001), t-IVT (r=-0.44, p&lt;0.001),Tei index (r=-0.43, p&lt;0.001) and NYHA class (r=-0.53, p&lt;0.001) had the highest correlationwith the 6-MWT distance. In multivariate analysis, only E/e’ ratio [0.800 (0.665-0.961),p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor 6-MWTperformance (&lt;300m). Conclusions: In HF, the higher the filling pressures and the more dyssynchronous the LV, thepoorer is the patient’s exercise capacity. Study III Methods: We studied 107 systolic HF patients; age 68±12 year, 25% females and measuredplasma NT-pro-BNP. Results: Over a follow-up period of 3718 months, t-IVT ≥12.3 sec/min, mean E/Em ratio≥10, log NT-pro-BNP levels ≥2.47 pg/ml and LV EF ≤32.5% predicted clinical events. Theaddition of t-IVT and NT-pro-BNP to conventional clinical and echocardiographic variablessignificantly improved the χ2 for the prediction of outcome from 33.1 to 38.0, (p&lt;0.001). Conclusions: Prolonged t-IVT adds to the prognostic stratification of patients with systolicHF. Study IV Methods: We studied 147 HF patients (61±11 year, 50.3% male) with 6-MWT.Results: The 6-MWT correlated with t-IVT (r=-0.49, p&lt;0.001) and Tei index (r=-0.43,p&lt;0.001) but not with any of the other clinical or echocardiographic parameters. Group Ipatients (&lt;300m) had lower Hb (p=0.02), lower EF (p=0.003), larger left atrium (p=0.02),thicker septum (p=0.02), lower A wave (p=0.01) and lateral wall a’ (p=0.047), longerisovolumic relaxation time (r=0.003) and longer t-IVT (p= 0.03), compared with Group II(&gt;300m). Only t-IVT ratio [1.257 (1.071-1.476), p=0.005], LV EF [0.947 (0.903-0.993),p=0.02], and E/A ratio [0.553 (0.315-0.972), p=0.04] independently predicted poor 6-MWTperformance. Conclusion: In HF, the limited 6-MWT is related mostly to severity of global LVdyssynchrony, more than EF or raised filling pressures. Study V Methods: We studied 47 healthy individuals (age 62±12 year, 24 female), arbitrarilyclassified into: M (middle age), S (seniors), and E (elderly). Results: Age strongly correlated with t-IVT (r=0.8, p&lt;0.001) and with Tei index (r=0.7,p&lt;0.001), E/A ratio (r=-0.6, p&lt;0.001), but not with global or segmental systolic function measurements or QRS duration. The normal upper limit of the t-IVT (95% CI) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively, being shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p&lt;0.001), E/Aratio (r=-0.56, p&lt;0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but notwith QRS. Conclusions: In normals, age is associated with exaggerated LV global dyssynchrony anddiastolic function disturbances, but systolic function remains unaffected. Study VI Methods: We studied 103 HF patients (67±12 year, 82.5% male) recruited for CRTtreatment. Results: Prolonged t-IVT [0.878 (0.802-0.962), p=0.005], long QRS duration [0.978 (0.960-0.996), p=0.02] and high tricuspid regurgitation pressure drop (TRPD) [1.047 (1.001-1.096),p=0.046] independently predicted response to CRT. A t-IVT ≥11.6 s/min was 67% sensitiveand 62% specific (AUC 0.69, p=0.001) in predicting CRT response. Respective values for aQRS ≥ 151ms were 66% and 62% (AUC 0.65, p=0.01). Combining the two variables had asensitivity of 67% but higher specificity of 88% in predicting CRT response. In atrialfibrillation (AF) patients, only prolonged t-IVT ≥11 s/min [0.690 (0.509-0.937), p=0.03]independently predicted CRT response with a sensitivity of 69% and specificity of 79% (AUC0.78, p=0.015). Conclusion: Combining prolonged t-IVT and broad QRS had higher specificity in predictingresponse to CRT, with the former the sole predictor of response in AF patients.

Purpose: Patients living with advanced heart failure experience dyspnea, fatigue, poor quality of life, depression and cognitive impairment which may threaten their ability to provide informed consent to undergo heart transplant (HTx) or mechanical support (LVAD). Using qualitative and quantitative methods, we asked how patients with advanced heart failure make decisions regarding HTx and LVAD. The variables chosen to reflect the elements of consent included quality of life and symptom severity (voluntariness), depression and cognitive impairment (capacity) and treatment preferences (decision-making). Methods: 76 patients enrolled in the quantitative arm completed the Minnesota Living with Heart Failure Questionnaire; Visual Analog scales for dyspnea, fatigue and overall health; Beck Depression Inventory; Montreal Cognitive Assessment; Standard Gamble and Time Tradeoff. Qualitative methods were used to discover concepts, relationships and decision-making processes described by 17 of the 76 patients considering HTx and LVAD. Results: Patients reported poor quality of life and high symptom severity scores which compelled them to consider surgery as a way to relieve unpleasant symptoms and improve quality of life. Although 30% of patients had evidence of depression and/or cognitive impairment, no patient was deemed incapable of decision-making. Patients were willing to take considerable risk (35%) and trade considerable time (4months) to improve their health. While heart failure-related concepts were important to the decision, entrustment emerged as the meaningful process for decision-making. Conclusions: Patients who participated in this study were capable of decision-making and understood the risks associated with the surgery. Voluntariness was diminished by disease but not absent, and decisions were free of coercion. These results suggest the entrustment model of decision-making is the dominant process for patients considering high-risk surgical procedures and meets criteria for informed consent. Understanding the process of decision-making will help clinicians support and enable treatment decisions made by patients living with advanced heart failure.

The definition of optimal selection criteria for maximizing the response rate to Cardiac Resynchronization Therapy (CRT) is still an issue under active debate. Recent clinical approaches propose a classification of patients into classes of mechanisms that could lead to heart failure and study their response to the therapy. In this line of research, the computation of a metric between the motion and deformation patterns of a given subject and well identified classes of CRT responders is considered in this thesis, as the basis of a new strategy to compute patient selection indexes. The thesis proposes first an improved design for the construction of statistical atlases of myocardial motion and deformation, and applies it to the characterization of populations of patients involved in CRT. The added-value of our approach is highlighted in a clinical study, applying the methodology to a large population of patients with a given pattern of dyssynchrony (septal flash) and understanding the link between its correction and CRT response. Finally, we propose a method to extend the analysis to the comparison of individuals to reference populations, either healthy or pathological, using manifold learning techniques to model a disease as progressive deviations from normality along a manifold structure, and demonstrate the potential of our method for inter-subject comparison in CRT patients. / La definición de un criterio óptimo para mejorar la respuesta a la Terapia de Resincronización Cardíaca (TRC) sigue siendo un debate abierto. Estudio clínicos recientemente publicados proponen clasificar pacientes según diversos mecanismos patofisiológicos que pueden inducir insuficiencia cardíaca y estudian su respuesta a la terapia. Siguiendo esta línea de investigación, esta tesis considera el cálculo de una distancia entre los patrones de movimiento y deformación de un individuo y las clases de respondedores a la TRC, siendo la base de una nueva estrategia para calcular índices para seleccionar pacientes. Esta tesis presenta primero un método para construir un atlas estadístico de movimiento y deformación miocárdica, y su aplicación posterior a la caracterización de poblaciones de potenciales candidatos a la TRC. El valor añadido de nuestro método se enfatiza en un estudio clínico, en el cual se aplica la metodología a una gran población de pacientes con un patrón específico de disincronía cardíaca (llamado septal flash), y se relaciona su corrección y la respuesta a la TRC. Finalmente, se extiende el método para comparar individuos a una población de referencia, sana o patológica, usando técnicas de manifold learning para representar una patología como una desviación progresiva de la normalidad, con una estructura no lineal específica, y se demuestra el potencial de nuestro método para comparar entre sí candidatos a la TRC.

Diss. Linköping : Linköpings universitet, 2004.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.