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Évolution Échocardiographique Et Prédicteurs De Progression De La Sténose Valvulaire Aortique

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Évolution Échocardiographique Et Prédicteurs De Progression De La Sténose Valvulaire Aortique Université de Montréal Évolution échocardiographique et prédicteurs de progression de la sténose valvulaire aortique par Adriana Benjamim de Oliveira Département de Sciences biomédicales Faculté de médecine Mémoire présenté à la Faculté des études supérieures en vue de l’obtention du grade de maîtrise ès sciences en Sciences Biomédicales option Recherche clinique Avril, 2014 © Adriana Benjamim de Oliveira, 2014 Université de Montréal Faculté des études supérieures Ce mémoire intitulé : Évolution échocardiographique et prédicteurs de progression de la sténose valvulaire aortique présenté par : Adriana Benjamim de Oliveira a été évalué par un jury composé des personnes suivantes : E. Marc Jolicoeur, président-rapporteur Jean-Claude Tardif, directeur de recherche Éric Rhéaume, co-directeur Jonathan Afilalo, membre du jury Résumé Introduction: L’utilisation clinique de biomarqueurs pour prédire la progression de la sténose valvulaire aortique (SVA) n’est pas encore validée à ce jour. Nous voulons évaluer des prédicteurs de la progression de la SVA d’étiologie dégénérative sur la valve aortique tricuspide. Méthodes: Nous avons identifié 126 cas avec SVA et ≥ 2 échocardiogrammes post-recrutement et 126 témoins appariés recrutés par la Biobanque de l’Institut de Cardiologie de Montréal. Nous avons collecté des données cliniques, échocardiographiques et génétiques de base et nous avons mesuré des biomarqueurs plasmatiques. L’évolution de la SVA a été établie par l’analyse des échocardiogrammes sériés et définie comme la variation moyenne par an des paramètres suivants: vitesse transvalvulaire aortique maximale, gradient transvalvulaire aortique moyen (GTAM), aire valvulaire aortique et aire valvulaire aortique indexée. Nous avons évalué l’association des données cliniques/échocardiographiques/génétiques (polymorphisme LPA rs10455872) avec la progression de la SVA et des biomarqueurs plasmatiques avec la présence et la progression de la SVA. Résultats: La durée moyenne de suivi a été de 2,4 ans. Selon des analyses multivariées concernant les données cliniques/échocardiographiques/LPA rs10455872, une fréquence cardiaque plus élevée (pour les patients plus agés et les hommes), le diabète (pour les hommes), et un plus grand GTAM au premier échocardiogramme sont associés à une évolution plus rapide de la SVA. La présence de régurgitation aortique au premier échocardiogramme est associée à une évolution plus lente de la SVA. L’analyse des biomarqueurs plasmatiques versus la présence et la progression de la SVA est en cours. Conclusion: Nos résultats indiquent que une fréquence cardiaque plus élevée, le diabète, et un plus grand GTAM au premier échocardiogramme sont associés avec une progression plus rapide de la SVA. Les résultats de cette étude pourraient contribuer à une approche plus personnalisée du suivi et du traitement de la SVA. Mots-clés: Sténose valvulaire aortique, biomarqueurs, fréquence cardiaque, diabète, gradient transvalvulaire aortique moyen, régurgitation aortique ii Abstract Introduction: The clinical use of biomarkers to predict the progression of aortic valve stenosis (AVS) is not yet validated. We want to evaluate potential predictors of the progression of degenerative AVS on tricuspid valve. Methods: We identified 126 cases with AVS and ≥ 2 echocardiograms post-recruitment and 126 paired controls recruited by the Montreal Heart Institute’s Biobank. We collected clinical, echocardiographic and genetic base data and measured plasma biomarkers. The AVS evolution was established by the analysis of the serial echocardiograms and defined as the mean variation per year of the following parameters: maximal aortic transvalvular velocity, mean aortic transvalvular gradient (MATG), aortic valve area and indexed aortic valve area. We evaluated the association of clinical, echocardiographic and genetic (LPA rs10455872 polymorphism) data with the AVS progression and plasma biomarkers with the AVS presence and progression. Results: The mean follow-up was 2.4 years. According to multivariate analysis concerning the clinical/echocardiographic/ LPA rs10455872 data, a higher heart rate (for older patients and males), diabetes mellitus (for males) and a greater MATG in the first echocardiogram are associated to a faster AVS evolution. The presence of aortic regurgitation in the first echocardiogram is associated to a slower AVS evolution. The analysis of plasma biomarkers versus the AVS presence and progression is ongoing. Conclusion: Our results indicate that a higher heart rate, diabetes mellitus, and a greater MATG are associated with faster AVS progression. The results of this study should contribute to a more personalized approach of the AVS follow-up and treatment. Keywords: Aortic valve stenosis, biomarkers, heart rate, diabetes mellitus, mean aortic transvalvular gradient, aortic regurgitation. iii Table des matières Résumé ............................................................................................................................................ ii Abstract .......................................................................................................................................... iii Table des matières .......................................................................................................................... iv Liste des Tableaux ....................................................................................................................... viii Liste des Figures ............................................................................................................................ ix Liste des sigles et des abréviations ................................................................................................ xi Dédicace ........................................................................................................................................ xv Remerciements ............................................................................................................................. xvi Introduction ..................................................................................................................................... 1 1. La valve aortique ..................................................................................................................... 1 1.1 Définition .................................................................................................................... 1 1.2 Anatomie macroscopique ............................................................................................ 3 1.3 Anatomie microscopique ............................................................................................ 5 1.4 Variantes anatomopathologiques ................................................................................ 7 2. Sténose valvulaire aortique (SVA) ......................................................................................... 9 2.1 Définition .................................................................................................................... 9 2.2 Physiopathologie ....................................................................................................... 10 2.3 Épidémiologie ........................................................................................................... 25 2.4 Présentation clinique ................................................................................................. 26 2.5 Diagnostic et suivi..................................................................................................... 30 2.6 Traitement ................................................................................................................. 50 3. Progression de la SVA .......................................................................................................... 59 3.1 Progression hémodynamique de la SVA .................................................................. 59 3.2 Biomarqueurs sériques versus la présence et la progression de la SVA ................... 63 4. La Biobanque de la Cohorte Génétique Hospitalière de l’Institut de Cardiologie de Montréal et l’étude principale « Aspects génétique et moléculaire de la sténose valvulaire aortique » ...... 66 4.1 La Biobanque de la Cohorte Génétique Hospitalière de l’Institut de Cardiologie de Montréal ................................................................................................................................ 66 iv 4.2 L’étude principale « Aspects génétiques et moléculaires de la sténose valvulaire aortique » .............................................................................................................................. 67 Objectifs ........................................................................................................................................ 69 1. Objectif principal .................................................................................................................. 69 1.1 Objectif(s) secondaire(s) ........................................................................................... 69 Méthodes détaillées ....................................................................................................................... 70 1. Recrutement et sélection des patients ................................................................................... 70 1.1 Critères d’inclusion ................................................................................................... 71 1.2 Critères d’exclusion
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