Aims To investigate whether there is evidence for distinct cardiac output (CO) based phenotypes in patients with chronic right heart failure associated with severe tricuspid regurgitation (TR) and to characterize their impact on TR treatment and outcome. Methods and results A total of 132 patients underwent isolated transcatheter tricuspid valve repair (TTVR) for functional TR at two centres. Patients were clustered according to k-means clustering into low [cardiac index (CI) < 1.7 L/min/m2], intermediate (CI 1.7–2.6 L/min/m2) and high CO (CI > 2.6 L/min/m2) clusters. All-cause mortality and clinical characteristics during follow-up were compared among different CO clusters. Mortality rates were highest for patients in a low (24%) and high CO state (42%, log-rank P < 0.001). High CO state patients were characterized by larger inferior vena cava diameters (P = 0.003), reduced liver function, higher incidence of ascites (P = 0.006) and markedly reduced systemic vascular resistance (P < 0.001) as compared to TTVR patients in other CO states. Despite comparable procedural success rates, the extent of changes in right atrial pressures (P = 0.01) and right ventricular dimensions (P < 0.001) per decrease in regurgitant volume following TTVR was less pronounced in high CO state patients as compared to other CO states. Successful TTVR was associated with the smallest prognostic benefit among low and high CO state patients. Conclusions Patients with chronic right heart failure and severe TR display distinct CO states. The high CO state is characterized by advanced congestive hepatopathy, a substantial decrease in peripheral vascular tone, a lack of response of central venous pressures to TR reduction, and worse prognosis. These data are relevant to the pathophysiological understanding and management of this important clinical syndrome. Graphical Abstract Proposed mechanism of hypercirculatory tricuspid regurgitation. Tricuspid regurgitation related backward failure causes liver congestion and dysfunction with portal hypertension and reduced washout of vasoactive substances. Consequent splanchnic and peripheral vasodilatation alongside with reduced renal blood flow results in renin–angiotensin–aldosterone system (RAAS) activation and sympathetic overactivation. The sympathetic drive and volume retention lead to further capacitance depletion and volume overload, eventually resulting in a high cardiac output state, with limited preload reduction and prognostic benefit following transcatheter tricuspid valve repair. The alterations in the graph should be interpreted as simultaneous interaction rather than a timeline. Continuous lines indicate findings in the present study. Dashed lines express currently accepted mechanistical considerations. AP, alkaline phosphatase; γGT, gamma-glutamyl-transferase; RA, right atrium; RV, right ventricle.

Plusieurs avancées exceptionnelles ont permis à un nombre grandissant d’enfants avec pathologies cardiaques complexes d’atteindre l’âge adulte. Ainsi, plus de patients développent maintenant des complications en lien avec leur maladie ou leurs antécédents chirurgicaux. Malheureusement, en raison de nombreux obstacles limitant la recherche en cardiopathie congénitale adulte, un écart de savoir perdure et freine l’optimisation des soins. En attendant le couplage de grands registres pédiatriques et adultes facilitant l’accès aux données existantes, les projets multicentriques indépendants demeurent essentiels. Cette thèse présente deux études multicentriques de cohorte comparant des techniques opératoires couramment utilisées dans le traitement de pathologies congénitales cardiaques complexes dans le but de promouvoir la santé des patients à long terme. La première étude visait à évaluer l’impact chronique du type de procédure de Fontan sur le risque thromboembolique. Pour ce projet nord-américain, 522 patients avec connexion atriopulmonaire (21.4%), tunnel latéral (41.8%) ou conduit extracardiaque (36.8%) ont été recrutés. À l’aide d’analyses multivariées contrôlant pour la décennie opératoire et les effets variables dans le temps de l’arythmie et de la thromboprophylaxie, l’étude a conclu à un plus faible risque de complications thromboemboliques systémiques (rapport des risques instantanés [RRI] : 0.20 ; intervalle de confiance [IC] à 95% : 0.04-0.97) et combinées (RRI : 0.34 ; IC à 95% : 0.13-0.91) avec le conduit extracardiaque. Ces résultats remettent en question la croyance populaire selon laquelle cette technique serait plus thrombogène en raison d’un grand contact avec du matériel synthétique et d’un débit limité par le calibre fixe du greffon. La deuxième étude avait pour but d’investiguer, auprès de patients avec tétralogie de Fallot ou sténose pulmonaire corrigée nécessitant une implantation de valve pulmonaire, l’efficacité immédiate et l’innocuité d’une intervention concomitante sur la valve tricuspide. Pour ce projet pancanadien, 542 patients ayant subi un remplacement isolé de la valve pulmonaire (66.8%) ou une chirurgie combinée des valves pulmonaire et tricuspide (33.2%) ont été enrôlés. À l’aide d’analyses multivariées, cette étude a révélé que la chirurgie combinée était associée à une plus grande réduction du grade de régurgitation tricuspidienne qu’un remplacement isolé de la valve pulmonaire (rapport de cotes [RC] : 0.44 ; IC à 95% : 0.25-0.77) sans une augmentation des complications périopératoires (RC : 0.85 ; IC à 95% : 0.46-1.57) ou du temps d’hospitalisation (ratio du taux d’incidence : 1.17 ; IC à 95% : 0.93-1.46). Ces résultats questionnent la pertinence d’une gestion conservatrice de l’insuffisance tricuspide sévère. De plus, ils confirment qu’une procédure ciblée peut améliorer de façon sécuritaire la fuite modérée au-delà de l’effet produit par la décharge du ventricule – une stratégie potentiellement avantageuse auprès de jeunes patients déjà à haut risque de défaillance cardiaque droite. En conclusion, avec une puissance statistique plus élevée que les études précédemment publiées, ces travaux ont permis une comparaison valide et pertinente de techniques opératoires couramment utilisées en chirurgie cardiaque congénitale, ce qui influencera possiblement la pratique. Ultimement, cette thèse souligne l’importance de promouvoir la collaboration afin de répondre aux besoins émergents des patients avec pathologies congénitales cardiaques complexes. / Outstanding technical advances have made possible for a growing number of infants with complex heart disease to survive into adulthood. Consequently, more patients are now living long enough to experience late complications related to their underlying pathology or sequelae from past interventions. However, due to the inherent challenges of carrying research in adult congenital heart disease, important knowledge gaps prevent further optimization of care. Waiting on broad linkage of pediatric and adult databases to facilitate access to data, stand-alone multicenter research initiatives remain essential. The current body of work presents two multicenter cohort studies which were designed to help improving the long-term health of patients with complex heart disease through a comparison of common operative techniques. The first study sought to evaluate the chronic impact of Fontan surgery type on the thromboembolic risk. This North American cohort enrolled 522 patients with univentricular palliation consisting of an atriopulmonary connection (21.4%), lateral tunnel (41.8%) or extracardiac conduit (36.8%). In multivariable analyses stratified by surgical decade and controlling for the time-varying effects of atrial arrhythmias and thromboprophylaxis, extracardiac conduits were independently associated with a lower risk of systemic (hazard ratio [HR]: 0.20 vs. lateral tunnel; 95% confidence interval [CI]: 0.04-0.97) and combined (HR: 0.34 vs. lateral tunnel; 95% CI: 0.13-0.91) thromboembolic events. These results cast doubt on the widely held notion that extracardiac conduits are potentially more thrombogenic than lateral tunnels by virtue of greater exposure to synthetic material and relative flow restriction through a fixed pathway. The second study investigated, in patients with repaired tetralogy of Fallot or equivalent disease undergoing a first pulmonary valve implant, the early effectiveness and safety of concomitant tricuspid valve intervention. This pan-Canadian cohort included 542 patients who underwent isolated pulmonary valve replacement (66.8%) or combined pulmonary and tricuspid valve surgery (33.2%). In multivariable analyses, combined surgery was associated with a greater reduction in tricuspid regurgitation grade than isolated pulmonary valve replacement (odds ratio [OR]: 0.44; 95% CI: 0.25-0.77) without an increase in early adverse events (OR: 0.85; 95% CI: 0.46-1.57) or hospitalization time (incidence rate ratio: 1.17; 95% CI: 0.93-1.46). These results strongly question the appropriateness of conservative management of severe tricuspid regurgitation at the time of pulmonary reintervention. Furthermore, they confirm that concomitant tricuspid valve intervention can safely improve moderate insufficiency beyond the effect of right ventricular offloading – a strategy likely worthwhile to adopt in a population of young adults already at high risk of right heart failure. In conclusion, with higher statistical power than previously published studies, the presented body of work allowed for a valid comparison of common surgical techniques used in congenital cardiac care, which will likely impact current practices. Ultimately, this thesis underlines the importance of fostering collaboration in order to meet the emerging health needs of patients with complex heart disease.