Cardiac remodeling in Ebstein's anomaly after Cone operation assessed by cardiovascular magnetic resonance

This doctoral work focuses on cardiac remodeling in patients with Ebstein’s anomaly (EA) undergoing Cone repair (CR), integrating different cardiovascular magnetic resonance (CMR) techniques and posing the premises for extending their clinical applicability even to pediatric patients requiring sedation. 1. Ambulatory Sedation for Pediatric CMR and Computed Tomography The first preliminary study demonstrates the feasibility and safety of ambulatory sedation for CMR and computed tomography (CT) in infants and toddlers with congenital heart disease (CHD), including EA. Ninety-one examinations in children younger than six years (median age 26 months) were analyzed. Most patients had severe CHD, 68% falling within the American Society of Anesthesiologists (ASA) Class IV; nonetheless, sedation performed with midazolam, propofol and S-ketamine enabled high-quality imaging with a low complication rate (3.3%), all events being reversible and without sequelae. Importantly, all but two children were discharged home the same day. These findings demonstrate that ambulatory sedation is safe and effective for high-quality cardiac imaging in experienced centers, provided that immediate in-hospital backup is available. This approach expands the feasibility of advanced imaging, including CMR, to pediatric and high-risk patients without the need for hospitalization. 2. Right Ventricular Strain Analysis by CMR-Feature-Tracking The second study explores myocardial mechanics beyond conventional volumetric evaluation through CMR-feature-tracking (CMR-FT) in 18 patients before and after CR. CMR-FT quantified global radial (GRS), circumferential (GCS), and longitudinal strain (GLS) of the functional right ventricle. Following CR, tricuspid regurgitation (TR) decreased dramatically (from 48% to 6%, p < 0.001). Along this, both right ventricular ejection fraction (RVEF) and right ventricular stroke volume (RVSV) significantly declined, reflecting the altered loading conditions after once valve competence is restored. In contrast, GRS and GCS improved significantly, while GLS decreased slightly, suggesting differential sensitivity of strain components to postoperative hemodynamics. These results suggest that GRS and GCS represent more load-independent parameters of intrinsic myocardial performance. The study confirms that CMR-FT is a powerful, non-invasive tool to detect subtle myocardial function changes in EA, providing a potential marker for postoperative monitoring and surveillance of right ventricular myocardial performance. 3. Ventricular Remodeling and Outcomes after Cone Repair The third study, presents one of the largest cohorts evaluated with CMR after CR for EA, including 54 patients with comprehensive pre- and postoperative CMR-examinations. Results confirm predominantly favorable ventricular remodeling, characterized by a significant reduction in right ventricular volumes, abolition of TR, and increase in left ventricular volumes and cardiac index (CI). Mortality was low (5% overall, 1.8% after 2011, one year after the technique was introduced), supporting both the safety and efficacy of Cone technique in specialized centers. Patients who died postoperatively were significantly older and had markedly increased right ventricular volumes with higher ratio between right ventricular and left ventricular end-diastolic volume (RVEDV/LVEDV ratio), indicating that advanced age and preoperative right ventricular dilation constitute strong predictors of mortality. In the survivor group, postoperative improvement of RVEDV/LVEDV ratio, confirmed the hemodynamic benefits of CR. Nevertheless, a consistent postoperative decrease in right RVEF was observed; this likely reflects the unmasking of intrinsic right-ventricular myocardial disease due to the overload that develops once the tricuspid valve has been made competent. A small but significant subset of survivors (12%) exhibited adverse remodeling (AR), defined as a postoperative increase in RVEDV/LVEDV ratio. These patients showed preoperative left ventricular volumes significantly larger than those with favorable remodeling (FR), suggesting that even patients with preserved left ventricular preload may develop suboptimal postoperative remodeling. Multivariate analysis confirmed larger right ventricular and left ventricular volumes and lower RVEF as independent predictors of death or AR. Overall, the study supports the view of EA not merely as a valvular disease but as a developmental cardiomyopathy involving both ventricles. While CR effectively corrects the valvular component, the underlying myocardial dysfunction may impact post-surgical prognosis. These findings underscore the need to intensify research in order to refine patient selection for surgery; extensive pre-operative tissue characterization to evaluate intrinsic myocardial disease, together with hemodynamic assessment to better define the pre-operative diastolic properties of both ventricles and interventricular interaction, could help achieve this goal. Together, these studies offer a comprehensive overview of the structural and functional response to CR in EA, highlighting the pivotal role of different CMR techniques in its assessment. Importantly, they integrate conventional volumetric analysis and CMR feature-tracking to characterize myocardial adaptation after surgery. This combined approach allows the identification of distinct patterns of postoperative remodeling - favorable and adverse - emphasizing the importance of cohort stratification, as global analyses may be misleading in such a heterogeneous disease. These findings provide both mechanistic insight and practical guidance for perioperative assessment and long-term follow-up in EA. Furthermore, by demonstrating the feasibility of performing advanced CMR in a pediatric population within an outpatient setting, this work lays the foundation for extending these approaches to younger patients, enabling earlier and more robust longitudinal evaluation. Although much remains to be understood before achieving an evidence-based and individualized risk stratification and management in the broad and complex spectrum of EA, these findings contribute a small but tangible step toward improving our comprehension of this rare condition.