L'objectif de ce travail était de mieux appréhender les mécanismes impliqués dans la réponse à la resynchronisation biventriculaire (BIV) en insistant sur la caractérisation du substrat électrique éligible à la thérapie et l'intérêt de la resynchronisation électrique. Nous avons démontré qu'il existe une relation forte entre l'asynchronisme électrique de base défini tant par l'ECG de surface que par cartographie détaillée de l'activation ventriculaire (ECM) et la réponse hémodynamique à la stimulation BIV. Par rapport à l'ECG de surface, l'ECM permet une caractérisation plus fine de l'asynchronisme électrique ventriculaire avec une meilleure prédiction de la réponse clinique à la stimulation BIV. La présence d'un asynchronisme de base minimum, en particulier d'un retard d'activation ventriculaire gauche (VG) par rapport au ventricule droit (typiquement >SOms), est un prérequis à l'efficacité de la thérapie. Les patients avec bloc de branche gauche présentent un haut degré d'asynchronisme et la stimulation BIV agit sur ce substrat par resynchronisation de l'activation électrique. A contrario, la stimulation BIV dégrade la séquence d'activation ainsi que l'hémodynamique des patients à QRS fins (dyssynchronie iatrogène). Les patients présentant un trouble de conduction aspécifique présentent des degrés variables d'asynchronie électrique et en conséquence des réponses contrastées à la stimulation BIV. De même, l'analyse ECM de l'asynchronisme des patients chroniquement stimulés sur le ventricule droit a permis de mettre en évidence des degrés variables de retard d'activation du VG. Si la resynchronisation électrique est garante d'une amélioration de la fonction cardiaque, d'autres mécanismes sont impliqués telle la redistribution du travail segmentaire au sein du myocarde ventriculaire. L'efficacité de la stimulation mono-VG implique une participation accrue du ventricule droit au travail global (interaction ventriculaire). / We aimed to characterize the electrical substrate amenable to biventricular pacing (BVP) and to assess the actual value of electrical resynchronization. We showed, both with respect to surface ECG and detailed ventricular electrocardiographic mapping (ECM), a strong relationship between the baseline electrical dyssnchrony and the hemodynamic response to BIV pacing. Compared with standard ECG, ECM allows a more detailed analysis of the ventricular dyssynchrony and better predicts clinical outcomes after BVP. A minimal amount of electrical dyssynchrony, in particular a sufficient LV activation delay relative to right ventricular activation, is a prerequisite to the hemodynamic response to BVP. Due to their advanced electrical dyssynchrony, patients with left bundle branch block present potential for BVP positive response which acts by electrical resynchronization. Conversely, BVP worsens the electrical activation (iatrogenic dyssynchrony) and hemodynamics in patients with narrow QRS suffering from insufficient electrical dyssynchrony at baseline. Patients with unspecified conduction disorders show variable levels of electrical dyssynchrony and as a consequence mixed results to BVP. Similarly, ECM reveals a variable degree of left ventricular activation delay in patients chronically paced in the right ventricle. Beside the electrical resynchronization, other mechanisms are involved in the cardiac pump function improvement such as the redistribution of the mechanical work over the right and left ventricles. Through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by single site LV pacing.

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.

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.

Introdução: O bloqueio atrioventricular congênito isolado (BAVCi) é raro e tem múltiplas apresentações clínicas. O implante de marca-passo cardíaco permanente (MP) é o tratamento de escolha, resultando em evolução clínica satisfatória para a maioria dos casos, porém, aproximadamente 10% deles apresentam remodelamento ventricular e insuficiência cardíaca grave. Objetivos: Estudar a evolução tardia de crianças e adultos jovens com BAVCi e estimulação crônica do ventrículo direito (VD), visando determinar: a prevalência de sinais clínicos e laboratoriais de insuficiência cardíaca e de remodelamento ventricular; a capacidade funcional; a qualidade de vida e fatores preditores de alterações clínicas, funcionais ou ecocardiográficas. Métodos: Estudo transversal realizado em coorte de portadores de BAVCi e MP implantado antes de 21 anos de idade com estimulação no VD há mais de um ano. Todos os indivíduos foram submetidos a avaliação clínica e laboratorial, da capacidade funcional, da qualidade de vida e a ecocardiograma. Mães e sujeitos da pesquisa foram investigados para doenças reumatológicas. Os dados foram armazenados no sistema REDCap (Research Electronic Data Capture) e analisados pelos programas SAS (Statistical Analysis System), SPSS (Statistical Package for the Social Sciences) e R Studio. A análise dos dados incluiu: análise univariada para pesquisa de associações entre variáveis preditoras e desfechos, coeficiente de correlação de Pearson e modelo de regressão linear multivariado. Resultados: De março/2010 a dezembro/2013, foram avaliados 63 indivíduos, 68% do sexo feminino, com idade de 1 a 40 anos, com MP por 13,4 ± 6,5 anos e estimulação do VD por 10,0 ± 5,4 anos. O modo de estimulação era atrioventricular em 55,6%, o percentual de estimulação de VD de 97,9 ± 4,2% e a duração do complexo QRS estimulado de 152,4 ± 20,1 ms. A maioria (88,9%) era assintomática e não utilizava medicamentos de ação cardiovascular. Maior tempo de MP (P= 0,013), maior tempo de estimulação do VD (P= 0,005), maior idade na inclusão no estudo (P= 0,032) ou menor fração de ejeção do ventrículo (FEVE) (P= 0,013) associaram-se com a presença de classe funcional II (NYHA) e/ou uso medicamentos. Os valores do peptídeo natriurético tipo B foram normais em todos os exames laboratoriais, mas houve alteração da proteína C reativa ultrassensível, fator de necrose tumoral alfa e interleucina-6 em 66%, 34% e 13% exames, respectivamente. A distância média percorrida no teste de caminha de seis minutos foi de 546,9 ± 76,2 metros (91,0 ± 12,5% do valor predito). Os escores médios da qualidade de vida foram 78,1 ± 17,7 para o \"Sumário Físico\" e 76,6 ± 17,1 para o \"Sumário Mental\" do questionário Short Form 36 (SF-36) e de 77,4 ± 18,5, para o \"Sumário Físico\" e de 77,7 ± 21,6 para o \"Sumário Psicossocial\", do Child Health Questionnaire - Parent Form 50 (CHQ-PF50). Diminuição da FEVE foi detectada em 39,7% e aumento do diâmetro diastólico do ventrículo esquerdo (DDVE) em 22,2% dos indivíduos. A idade mais avançada no primeiro implante de MP se correlacionou negativamente com menor FEVE (r= -0,302; P= 0,016); a duração do complexo QRS estimulado (r= 0,447; P= 0,002) e maior tempo sob estimulação do VD (r= 0,416; P= 0,007) se correlacionaram positivamente ao aumento do DDVE. Foi detectada dissincronia ventricular em 60,3% dos indivíduos. O retardo da ativação eletromecânica intraventricular esquerda foi de 86,5 ± 56,9 ms e interventricular, de 141,9 ± 88 ms. Contudo, não houve correlação com os fatores estudados. Autoanticorpos anti-Ro/SSA foram detectados em 18 (32,1%) mães, com associação entre idade no momento do implante do MP (P= 0,032) e uso de MP ventricular no momento do estudo (P= 0,022). A regressão linear multivariada confirmou a correlação entre a idade no momento do implante do MP com a FEVE (P= 0,016), da duração do complexo QRS estimulado (P= 0,004) e do tempo sob estimulação do VD (P= 0,014) com o DDVE. Conclusões: A prevalência de manifestações clínicas e laboratoriais de insuficiência cardíaca foi baixa; por outro lado, a de remodelamento ventricular esquerdo foi elevada. A capacidade funcional foi satisfatória, assim como a qualidade de vida, nos aspectos físicos e emocionais. Idade mais avançada no primeiro implante de MP, maior tempo sob estimulação cardíaca e complexo QRS estimulado mais alargado foram fatores independentes de remodelamento ventricular e/ou de manifestação de insuficiência cardíaca / Introduction: Isolated congenital atrioventricular block (iCAVB) is a rare condition with multiple clinical presentations. Permanent cardiac pacing is the most effective therapy for this population resulting in satisfactory long-term outcomes. However, approximately 10% of patients may have ventricular remodeling and severe heart failure. Objectives: To study the long-term effects of chronic right ventricular (RV) pacing in children and young adults with iCAVB in order to determine: prevalence of clinical and laboratory signs of heart failure and ventricular remodeling, functional capacity, quality of life and predictors of clinical, functional or echocardiographic abnormalities. Methods: Cross-sectional study of a cohort of iCAVB patients with <= 21 years old at initial pacemaker (PM) implantation and single or dual-chamber pacing in a unique RV site for a minimum of one year. All subjects underwent clinical and laboratory assessment, functional capacity, quality of life and echocardiogram. Mothers and research subjects were investigated for rheumatic diseases. Data were stored in REDCap (Research Electronic Data Capture) system and analyzed by SAS (Statistical Analysis System), SPSS (Statistical Package for the Social Sciences) and R Studio programs. Data analysis included: univariate analysis for associations between predictor variables and outcomes, Pearson correlation coefficient and linear regression multivariate model. Results: Between March/2010 and December/2013, we evaluated 63 subjects aged 1-40 years old, 68% female, under PM for 13.4 ± 6.5 years and under RV pacing for 10.0 ± 5.4 years. Pacing mode was atrioventricular in 55.6%, percentage of RV pacing was 97.9 ± 4.2% and paced QRS duration was 152.4 ± 20.1 ms. Overall, the majority (88.9%) were asymptomatic and did not use cardiovascular drugs. Longer time under PM (P= 0.013), or even under RV pacing (P= 0.005), higher age at study inclusion (P= 0.032) and lower left ventricular ejection fraction (LVEF) (P= 0.013) were associated with functional class II (NYHA) and / or drug use. B-natriuretic peptide values were normal in all tests. C reactive protein ultrasensitive, tumor necrosis factor alfa and interleukin-6 were increased in 66%, 34% and 13% tests, respectively. The mean walked distance in the sex minute walk test was 546.9 ± 76.2 meters (91.0 ± 12.5% of the predicted value). Mean scores of quality of life were 78.1 ± 17.7 for \"Physical Summary\" and 76.6 ± 17.1 for \"Mental Summary\" in the Short Form 36 (SF-36) and 77.4 ± 18.5 for \"Physical Summary\" and 77.7 ± 21.6 for \"Psychosocial Summary\", of Child Health Questionnaire - Parent Form 50 (CHQ-PF50). Decreased LVEF was detected in 39.7% and increased left ventricular end-diastolic diameter (LVDD) in 22.2% of subjects. Higher age at the first PM implant was negatively correlated with lower LVEF (r= -0.302; P= 0.016); paced QRS duration (r= 0.447; P= 0.002) and time under RV pacing (r= 0.416; P= 0.007) were positively correlated with LVDD. Ventricular dyssynchrony was detected in 60.3 % of individuals. Intra-left ventricular electromechanical delay was 86.5 ± 56.9 ms and interventricular was 141.9 ± 88 ms. However, ventricular dyssynchrony was not correlated with the studied variables. Autoantibodies anti-SSA/Ro were detected in 18 (32.1%) mothers. There was association between age at PM implant (P= 0.032) and use of ventricular PM at the time of the study (P= 0.022) and presence of anti-SSA/Ro. Multivariate linear regression showed significant correlation between age at PM implant with LVEF (P= 0.016); and paced QRS duration (P= 0.005) and time under RV pacing (P= 0.014) with LVDD. Conclusions: Clinical and laboratorial manifestations of heart failure presented low prevalence in this population. On the other hand, the prevalence of left ventricular remodeling was high. Functional capacity was adequate, as well as quality of life, in both physical and emotional aspects. Higher age at first PM implant, longer time under pacing and wider paced QRS duration were independent factors of ventricular remodeling and/or manifestation of heart failure

Introdução: O bloqueio atrioventricular congênito isolado (BAVCi) é raro e tem múltiplas apresentações clínicas. O implante de marca-passo cardíaco permanente (MP) é o tratamento de escolha, resultando em evolução clínica satisfatória para a maioria dos casos, porém, aproximadamente 10% deles apresentam remodelamento ventricular e insuficiência cardíaca grave. Objetivos: Estudar a evolução tardia de crianças e adultos jovens com BAVCi e estimulação crônica do ventrículo direito (VD), visando determinar: a prevalência de sinais clínicos e laboratoriais de insuficiência cardíaca e de remodelamento ventricular; a capacidade funcional; a qualidade de vida e fatores preditores de alterações clínicas, funcionais ou ecocardiográficas. Métodos: Estudo transversal realizado em coorte de portadores de BAVCi e MP implantado antes de 21 anos de idade com estimulação no VD há mais de um ano. Todos os indivíduos foram submetidos a avaliação clínica e laboratorial, da capacidade funcional, da qualidade de vida e a ecocardiograma. Mães e sujeitos da pesquisa foram investigados para doenças reumatológicas. Os dados foram armazenados no sistema REDCap (Research Electronic Data Capture) e analisados pelos programas SAS (Statistical Analysis System), SPSS (Statistical Package for the Social Sciences) e R Studio. A análise dos dados incluiu: análise univariada para pesquisa de associações entre variáveis preditoras e desfechos, coeficiente de correlação de Pearson e modelo de regressão linear multivariado. Resultados: De março/2010 a dezembro/2013, foram avaliados 63 indivíduos, 68% do sexo feminino, com idade de 1 a 40 anos, com MP por 13,4 ± 6,5 anos e estimulação do VD por 10,0 ± 5,4 anos. O modo de estimulação era atrioventricular em 55,6%, o percentual de estimulação de VD de 97,9 ± 4,2% e a duração do complexo QRS estimulado de 152,4 ± 20,1 ms. A maioria (88,9%) era assintomática e não utilizava medicamentos de ação cardiovascular. Maior tempo de MP (P= 0,013), maior tempo de estimulação do VD (P= 0,005), maior idade na inclusão no estudo (P= 0,032) ou menor fração de ejeção do ventrículo (FEVE) (P= 0,013) associaram-se com a presença de classe funcional II (NYHA) e/ou uso medicamentos. Os valores do peptídeo natriurético tipo B foram normais em todos os exames laboratoriais, mas houve alteração da proteína C reativa ultrassensível, fator de necrose tumoral alfa e interleucina-6 em 66%, 34% e 13% exames, respectivamente. A distância média percorrida no teste de caminha de seis minutos foi de 546,9 ± 76,2 metros (91,0 ± 12,5% do valor predito). Os escores médios da qualidade de vida foram 78,1 ± 17,7 para o \"Sumário Físico\" e 76,6 ± 17,1 para o \"Sumário Mental\" do questionário Short Form 36 (SF-36) e de 77,4 ± 18,5, para o \"Sumário Físico\" e de 77,7 ± 21,6 para o \"Sumário Psicossocial\", do Child Health Questionnaire - Parent Form 50 (CHQ-PF50). Diminuição da FEVE foi detectada em 39,7% e aumento do diâmetro diastólico do ventrículo esquerdo (DDVE) em 22,2% dos indivíduos. A idade mais avançada no primeiro implante de MP se correlacionou negativamente com menor FEVE (r= -0,302; P= 0,016); a duração do complexo QRS estimulado (r= 0,447; P= 0,002) e maior tempo sob estimulação do VD (r= 0,416; P= 0,007) se correlacionaram positivamente ao aumento do DDVE. Foi detectada dissincronia ventricular em 60,3% dos indivíduos. O retardo da ativação eletromecânica intraventricular esquerda foi de 86,5 ± 56,9 ms e interventricular, de 141,9 ± 88 ms. Contudo, não houve correlação com os fatores estudados. Autoanticorpos anti-Ro/SSA foram detectados em 18 (32,1%) mães, com associação entre idade no momento do implante do MP (P= 0,032) e uso de MP ventricular no momento do estudo (P= 0,022). A regressão linear multivariada confirmou a correlação entre a idade no momento do implante do MP com a FEVE (P= 0,016), da duração do complexo QRS estimulado (P= 0,004) e do tempo sob estimulação do VD (P= 0,014) com o DDVE. Conclusões: A prevalência de manifestações clínicas e laboratoriais de insuficiência cardíaca foi baixa; por outro lado, a de remodelamento ventricular esquerdo foi elevada. A capacidade funcional foi satisfatória, assim como a qualidade de vida, nos aspectos físicos e emocionais. Idade mais avançada no primeiro implante de MP, maior tempo sob estimulação cardíaca e complexo QRS estimulado mais alargado foram fatores independentes de remodelamento ventricular e/ou de manifestação de insuficiência cardíaca / Introduction: Isolated congenital atrioventricular block (iCAVB) is a rare condition with multiple clinical presentations. Permanent cardiac pacing is the most effective therapy for this population resulting in satisfactory long-term outcomes. However, approximately 10% of patients may have ventricular remodeling and severe heart failure. Objectives: To study the long-term effects of chronic right ventricular (RV) pacing in children and young adults with iCAVB in order to determine: prevalence of clinical and laboratory signs of heart failure and ventricular remodeling, functional capacity, quality of life and predictors of clinical, functional or echocardiographic abnormalities. Methods: Cross-sectional study of a cohort of iCAVB patients with <= 21 years old at initial pacemaker (PM) implantation and single or dual-chamber pacing in a unique RV site for a minimum of one year. All subjects underwent clinical and laboratory assessment, functional capacity, quality of life and echocardiogram. Mothers and research subjects were investigated for rheumatic diseases. Data were stored in REDCap (Research Electronic Data Capture) system and analyzed by SAS (Statistical Analysis System), SPSS (Statistical Package for the Social Sciences) and R Studio programs. Data analysis included: univariate analysis for associations between predictor variables and outcomes, Pearson correlation coefficient and linear regression multivariate model. Results: Between March/2010 and December/2013, we evaluated 63 subjects aged 1-40 years old, 68% female, under PM for 13.4 ± 6.5 years and under RV pacing for 10.0 ± 5.4 years. Pacing mode was atrioventricular in 55.6%, percentage of RV pacing was 97.9 ± 4.2% and paced QRS duration was 152.4 ± 20.1 ms. Overall, the majority (88.9%) were asymptomatic and did not use cardiovascular drugs. Longer time under PM (P= 0.013), or even under RV pacing (P= 0.005), higher age at study inclusion (P= 0.032) and lower left ventricular ejection fraction (LVEF) (P= 0.013) were associated with functional class II (NYHA) and / or drug use. B-natriuretic peptide values were normal in all tests. C reactive protein ultrasensitive, tumor necrosis factor alfa and interleukin-6 were increased in 66%, 34% and 13% tests, respectively. The mean walked distance in the sex minute walk test was 546.9 ± 76.2 meters (91.0 ± 12.5% of the predicted value). Mean scores of quality of life were 78.1 ± 17.7 for \"Physical Summary\" and 76.6 ± 17.1 for \"Mental Summary\" in the Short Form 36 (SF-36) and 77.4 ± 18.5 for \"Physical Summary\" and 77.7 ± 21.6 for \"Psychosocial Summary\", of Child Health Questionnaire - Parent Form 50 (CHQ-PF50). Decreased LVEF was detected in 39.7% and increased left ventricular end-diastolic diameter (LVDD) in 22.2% of subjects. Higher age at the first PM implant was negatively correlated with lower LVEF (r= -0.302; P= 0.016); paced QRS duration (r= 0.447; P= 0.002) and time under RV pacing (r= 0.416; P= 0.007) were positively correlated with LVDD. Ventricular dyssynchrony was detected in 60.3 % of individuals. Intra-left ventricular electromechanical delay was 86.5 ± 56.9 ms and interventricular was 141.9 ± 88 ms. However, ventricular dyssynchrony was not correlated with the studied variables. Autoantibodies anti-SSA/Ro were detected in 18 (32.1%) mothers. There was association between age at PM implant (P= 0.032) and use of ventricular PM at the time of the study (P= 0.022) and presence of anti-SSA/Ro. Multivariate linear regression showed significant correlation between age at PM implant with LVEF (P= 0.016); and paced QRS duration (P= 0.005) and time under RV pacing (P= 0.014) with LVDD. Conclusions: Clinical and laboratorial manifestations of heart failure presented low prevalence in this population. On the other hand, the prevalence of left ventricular remodeling was high. Functional capacity was adequate, as well as quality of life, in both physical and emotional aspects. Higher age at first PM implant, longer time under pacing and wider paced QRS duration were independent factors of ventricular remodeling and/or manifestation of heart failure