Thèse de doctorat : Médecine. Cardiologie : Nantes : 2005. / Bibliogr.

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The Cardiology Brazilian Society believes that the valve disease represents a significant proportion of hospital admissions for cardiovascular disease. Patients who undergo invasive procedures, related to heart valve disease, require a multiprofessional monitoring. This is a qualitative and quantitative study that aims to investigate what the effects of Music Therapy on the levels of anxiety and stress of patients with heart prosthesis are. Patients older than eighteen, who had expressed their acceptance by the Term of Free and Informed Consent, which did not make use of psychotropic drugs and were not going through another non-pharmacological therapy, were included. The research was developed at the Serviço de Cardiologia do Hospital das Clínicas da Universidade Federal de Goiás (Cardiology Service, Hospital das Clinicas, Federal University of Goiás). The following data collection instruments were used: music therapeutics form, scale for stress evaluation, trace-state anxiety inventory, session reports, audio and / or video. The music therapy process, in a humanistic perspective, was developed by music therapist / researcher, using specific techniques of Musicotherapy in the course of ten weeks. A group of three female patients, aged 29 to 44 attended all phases of the screening. It was evident that Musicotherapy helped reduce the stress and anxiety of the participating patients. The chosen songs and testimonies at the end of the consultations expressed internal contents and showed feelings such as; suffering, overcoming and resilience among the participants. Regarding quantitative data, there was an improvement, but without statistically significant differences. Musicotherapy may be among the non-drug treatment options for patients, who underwent implantation of metal / biological heart valve, to reduce stress and anxiety. / As doenças cardiovasculares constituem uma das principais causas de morte em vários países do mundo. A Sociedade Brasileira de Cardiologia considera que a doença valvar representa uma significativa parcela das internações por doença cardiovascular. Os pacientes que passam por procedimentos invasivos relacionados à valvopatias necessitam de um acompanhamento multiprofissional. Este é um estudo de metodologia mista, quali-quantitativo, desenvolvido a partir de uma pesquisaintervenção com aplicação de avaliação quantitativa (dentro de uma perspectiva de antes e depois) e uma análise fenomenológica do processo musicoterapêutico vivenciado. Tem como principal objetivo investigar quais os efeitos da Musicoterapia nos níveis de ansiedade e de estresse de pacientes com prótese cardíaca. Foi aprovado pelo Comitê de Ética em Pesquisa do Hospital das Clínicas da Universidade Federal de Goiás - HC/UFG. Foram incluídos pacientes maiores de dezoito anos, que expressaram sua aceitação através do Termo de Consentimento Livre e Esclarecido, que não fizessem uso de psicotrópicos e que não estavam passando por outra terapia não farmacológica. A pesquisa foi desenvolvida no Serviço de Cardiologia do HC/UFG. Para a coleta de dados foram utilizados os seguintes instrumentos: ficha musicoterapêutica, escala para avaliação de estresse, inventário de ansiedade traçoestado, relatórios de sessões, áudios e/ou vídeos. O processo musicoterapêutico foi desenvolvido pela musicoterapeuta/pesquisadora, utilizando técnicas específicas da Musicoterapia no decorrer de dez semanas. Um grupo de três pacientes do sexo feminino, com idades entre 29 e 44 anos participou de todas as fases do estudo. Evidenciou-se que a Musicoterapia contribuiu para a redução do estresse e da ansiedade das pacientes participantes. A partir da análise qualitativa das sessões, revelou-se que as canções trazidas e os depoimentos no final dos atendimentos expressaram conteúdos internos e evidenciaram sentimentos como sofrimento, superação e resiliência entre as participantes. Com relação aos dados quantitativos, houve melhora, mas sem diferenças estatisticamente significantes. Concluiu-se que a Musicoterapia pode estar entre as possibilidades de tratamento não medicamentoso dos pacientes submetidos ao implante de válvula cardíaca metálica/biológica visando reduzir o estresse e a ansiedade.

Un lien entre certaines dysfonctions du système sérotoninergique et la survenue de valvulopathies a été suggéré par les lésions valvulaires observées au cours de l’utilisation chronique de certains agonistes des récepteurs 5-HT2 (dérivés de l’ergot de seigle, fenfluramine) et les atteintes tumorales carcinoïdes (qui entrainent une augmentation des taux de 5-HT circulante). Les lésions dégénératives associent une fibrose, une sténose et/ou une régurgitation des valves pouvant conduire à de nombreuses complications cardiovasculaires. À l’heure actuelle, il n’existe aucune thérapeutique pouvant freiner ou faire régresser les lésions. Nos travaux démontrent à partir de modèles animaux et cellulaires, l’implication effective des récepteurs 5-HT2B et 5-HT2A dans l’initiation des lésions. L’analyse histologique des valves à partir de nos modèles animaux a révélé la contribution des cellules endothéliales au cours des stades précoces. Ces cellules sont des progéniteurs endothéliaux (CD34+) recrutés à partir de la moelle au sein de la valve sous la stimulation des récepteurs 5-HT2 et par un mécanisme intracellulaire impliquant la eNOS. Des travaux ultérieurs permettront de mieux caractériser les différents types cellulaires et les biomarqueurs d’initiation du processus afin de déterminer de nouvelles pistes thérapeutiques. / Several studies have reported a strong correlation between the development of cardiac valve injury and some dysfunctions of the serotonergic system. Valve lesions are observed during the chronic use of some 5-HT2 receptors agonists (ergot derivates or fenfluramine derivatives) or are secondary to metastatic carcinoid tumours (with increased circulating 5-HT amount). These lesions show fibrosis, with thickened leaflets, valves stenosis and/or regurgitation followed by several cardiovascular complications. There is no medical treatment to stop or alter the natural course of the lesions. Surgical replacement by prosthesis is the only effective therapy. Our study based on animal and cellular pharmacological models, demonstrates the serotonergic system contribution through 5-HT2B and 5-HT2A receptors in the pathogenesis of valve degeneration. Histological analysis of the lesions reveals the contribution of endothelial cells to the initiation process. These cells are probably endothelial progenitors (CD34+) recruited inside the valve implying a NO-dependent mechanism. Further studies will characterize the specific cells to find biomarkers of valve remodelling initiation and at term, will identify best therapeutic targets around the serotonergic system.

L’hypothèse d’un lien entre valvulopathies et surexpression du système sérotoninergique fait suite aux lésions valvulaires observées lors de tumeurs carcinoïdes (taux sanguins de 5-HT élevés) et lors de l’utilisation chronique d’agonistes sérotoninergiques 5-HT2 (comme les dérivés de l’ergot de seigle, les fenfluramines). Le dogme actuel repose sur un effet prolifératif de la sérotonine, activant des cellules résidentes valvulaires, mais ne suffit pas à expliquer la dégénérescence de bioprothèses acellulaires. Nos travaux ont permis d’identifier des cellules progénitrices endothéliales (CD34+/CD309+), exprimant les récepteurs 5-HT2A et 5-HT2B, au sein de lésions valvulaires humaines aortiques et mitrales, quelle que soit l’étiologie de leur dégénérescence. Ils ont permis de mettre en évidence un rôle double de la sérotonine dans la dégénérescence valvulaire : 1) la stimulation des récepteurs 5-HT2B contribue à la mobilisation sanguine des progéniteurs CD34+ (recrutés à partir de la moelle osseuse, et migrant dans le tissu valvulaire), 2) le rôle des récepteurs 5-HT2 dans la transdifférenciation des progéniteurs endothéliaux en cellules activées, au sein de la matrice valvulaire. La suite de ce travail permettra de développer 1) un biomarqueur prédictif d’atteinte valvulaire, dans des populations à haut risque, 2) de développer un modèle cellulaire de valvulopathie pour étudier les mécanismes impliqués dans le remodelage valvulaire et leurs voies de signalisation, et 3) de déterminer des cibles thérapeutiques autour du système sérotoninergique, permettant de ralentir la progression des lésions et retarder l’exérèse chirurgicale, seule alternative actuelle.Abstract / Several studies have established an association between some cardiac valve injuries and overexpression of the serotonergic system. Valve lesions are observed following carcinoid tumours (with high blood levels of 5-HT) and during the chronic use of 5-HT2 serotonergic agonists (ergot derivatives or fenfluramines). The current dogma is based on a mitogenic effect of serotonin, by activating 5-HT2B receptors, leading to resident valvular cells proliferation, but does not explain the degeneration of acellular cardiac bioprosthesis. Our work identified endothelial progenitor cells (CD34 + / CD309 +), expressing 5-HT2A and 5-HT2B receptors, in human aortic and mitral valve lesions, regardless of the etiology of their degeneration. Our work highlights the dual role of serotonin in valvular degeneration: 1) stimulation of the 5-HT2B receptor contributes to blood mobilization of CD34+ progenitors (recruited from the bone marrow, and migrating in the valve tissue), 2) the role of 5-HT2 receptors in the transdifferentiation of endothelial progenitor cells in activated valvular cells. The results of this work could drive to the development of 1) a predictive biomarker of cardiac valve injuries in high-risk populations, 2) a model to study heart valve disease cellular and molecular mechanisms, and 3) identify therapeutic targets around the serotonergic system, to slower the progression of the lesions and delay surgical replacement, the only current alternative.