Loeys-Dietz syndrome (LDS) patients demonstrate heightened risk of distal thoracic aortic events after valve-sparing aortic root replacement (VSARR). This study assesses the clinical risks and hemodynamic consequences of a prophylactic aortic arch replacement strategy in LDS and characterizes smooth muscle cell (SMC) phenotype in LDS aneurysmal and normal-sized downstream aorta.Patients with genetically confirmed LDS (n=8) underwent prophylactic aortic arch replacement during VSARR. 4D flow magnetic resonance imaging (MRI) studies were performed in n=4 LDS patients (VSARR+arch) and compared with both contemporary Marfan syndrome patients (VSARR only, n=5) and control patients (without aortopathy, n=5). Aortic tissues from n=4 LDS patients and n=2 organ donors were processed for anatomically segmented single-cell RNA sequencing (scRNAseq) and histologic assessment.LDS VSARR+arch patients had no deaths, major morbidity, or aortic events in median 2.00 years follow-up. 4D-MRI demonstrated altered flow parameters in post-operative aortopathy patients relative to controls, but no clear deleterious changes attributable to arch replacement. Integrated analysis of aortic scRNAseq data (>49,000 cells) identified a continuum of abnormal SMC phenotypic modulation in LDS defined by reduced contractility and enriched extracellular matrix synthesis, adhesion receptors, and transforming growth factor-beta signaling. These 'modulated SMCs' populated the LDS tunica media with gradually reduced density from the overtly aneurysmal root to the non-dilated arch.LDS patients demonstrated excellent surgical outcomes without overt downstream flow or shear stress disturbances after concomitant VSARR+arch operations. Abnormal SMC-mediated aortic remodeling occurs within the normal diameter, clinically at-risk LDS arch segment. These initial clinical and pathophysiologic findings support concomitant arch replacement in LDS.
View details for DOI 10.1016/j.jtcvs.2023.07.023
View details for PubMedID 37500053