Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Open

Natural History and Consequences of Aortic Dilatation in Children with Conotruncal Malformations

Aditya Sengupta, MD


Background: Aortic or neo-aortic root and ascending aortic dilatation are common sequelae of conotruncal cardiac malformations in children. Gap: The natural history of pathologic aortic dilatation in children with conotruncal malformations is incompletely understood, with adverse implications for clinical management of the consequences of aortic root dilatation. Hypotheses: We hypothesize that 1) echocardiographically-derived aortic dimensions can be used to develop z-score equations that are adjusted for various patient-related variables; 2) nomograms derived for children with conotruncal malformations using the aforementioned z-scores are significantly different from that of the normal age-matched population, and a subset of children with conotruncal malformations display high-risk behavior in longitudinal z-score analyses; and 3) high-risk patterns of aortic root dilatation are significantly associated with the occurrence of adverse clinical events. Methods: A single-center, retrospective review of all patients who underwent primary repair of tetralogy of Fallot (TOF), truncus arteriosus (TA), and dextro-transposition of the great arteries (dTGA; i.e., the arterial switch operation) was performed. Patients were included if they survived to discharge free of transplantation and had at least two follow-up echocardiograms with pertinent aortic root dimension data. For each of the aforementioned conotruncal malformations, intrinsic anatomy was categorized as follows: 1) TOF, pulmonary stenosis (TOF-PS) and pulmonary atresia (TOF-PA); 2) TA, bicuspid, tricuspid, or quadricuspid truncal valve; 3) dTGA, dTGA with intact ventricular septum (dTGA-IVS), dTGA with ventricular septal defect (dTGA-VSD), and double-outlet right ventricle-TGA type (DORV-TGA). Echocardiographically-determined aortic or neo-aortic diameters and derived z-scores were measured at the annulus, sinus of Valsalva (SoV), and sinotubular junction (STJ) just before repair (baseline) and throughout clinical follow-up. Linear mixed effects models, comparing assessed trends in aortic diameters and z-scores over time. Results: The analytic cohort included 2205 patients with TOF, 193 patients with TA, and 1359 patients with dTGA. Among patients with TOF, at baseline, TOF-PA patients had larger diameters and z-scores at the annulus, SoV, and STJ, compared to TOF-PS patients (all p<0.05). Over time, TOF-PA patients demonstrated relatively greater annular (p=0.020), SoV (p<0.001), and STJ (p<0.001) dilatation. Patients with ≥75th percentile root growth rates had a higher incidence of at least moderate aortic regurgitation (p<0.001) and aortic valve repair or replacement (p=0.045). Among patients with TA, at baseline, relative to patients with tricuspid anatomy, bicuspid patients displayed larger SoV (p=0.003) and STJ (p=0.029) diameters, while quadricuspid patients had larger STJ diameters (p=0.004). Over time, the bicuspid and quadricuspid cohorts demonstrated comparatively greater annular dilatation (both p<0.05). Patients with root growth rates in the ≥75th percentile had a higher incidence of moderate-severe truncal regurgitation (p=0.037) and truncal valve repair or replacement (p=0.002). Among patients with dTGA, at baseline, there were no differences in annular, SoV, or STJ diameters between dTGA-IVS patients and dTGA-VSD or DORV-TGA patients. At 30 years, DORV-TGA patients had significantly larger diameters at the annulus (p<0.001), SoV (p=0.039), and STJ (p=0.041) relative to dTGA-IVS patients. Impact: The use of normative aortic dimensions may clinicians to better understand the natural history of aortic or neo-aortic root dilatation in children with conotruncal malformations, and thereby assess the optimal timing of eventual surgical or medical therapy for the complications of pathologic aortic dilatation.