Clinical Heterogeneity in Coarctation of the Aorta: Data-Driven Morbidity Sub-Phenotypes from a Nationwide Registry

Background/Objectives: Coarctation of the aorta (CoA) is associated with lifelong risks of residual or recurrent arch obstruction, hypertension, ventricular remodeling, and aortic-valve disease. We characterized documented morbidity and procedure-entry burden in a nationwide CoA registry cohort and assessed recurring morbidity patterns and age-dependent sex differences. Methods: Patients with CoA as the primary congenital diagnosis were identified in the German National Register for Congenital Heart Defects (NRCHD). Congenital, acquired cardiovascular, and extracardiac diagnoses, composite morbidity indicators, and procedure-source entries were analyzed descriptively and by age, CHD complexity, documented bicuspid aortic-valve (BAV) status, and sex. Exploratory latent class analysis characterized recurring cross-sectional morbidity patterns, and logistic regression assessed sex-by-age interactions. Results: Among 2720 patients (61.1% male; median age 17.85 years), BAV was documented in 34.4%, and a specific aortic-valve morphology in 65.6%. Arch-obstruction and pressure-load burden were documented in 27.7% and 27.2%, respectively, and were more frequent in older age groups. At least one operation- or catheter-intervention-source entry was present in 82.1% of patients. Five latent classes were identified: low documented burden (51.8%), arch-hypertension/pressure-load (11.4%), complex multilevel (18.9%), BAV/valve-aortopathy (13.1%), and systemic-hypertension/recurrent-obstruction (4.7%). Classification entropy was 0.661, and 25.3% of patients had a maximum posterior class probability below 0.70. Male sex was associated with higher pressure-load burden, and the sex-by-age interaction was significant in restricted cubic spline models (p = 0.004), whereas corresponding interactions were not supported for arch-obstruction burden or aortic-valve dysfunction excluding BAV morphology. Conclusions: CoA in routine clinical care is not a uniform condition but encompasses recurring patterns of documented morbidity centered on valve-aortopathy, complex congenital anatomy, and pressure-load or recurrent-obstruction disease. Documented BAV marked a particularly strong valve-morbidity phenotype, while pressure-load morbidity showed a distinct age-dependent association with sex. These findings provide a clinically interpretable framework for phenotype-oriented lifelong follow-up and future longitudinal validation, while reflecting registry-documented rather than systematically screened morbidity.