Coarctation Duration and Severity Predict Risk of Hypertension Precursors in a Preclinical Model and Hypertensive Status Among Patients

Abstract

BACKGROUND: Coarctation of the aorta (CoA) often leads to hypertension) posttreatment. Evidence is lacking for the current >20 mm Hg peak-to-peak blood pressure (BP) gradient (BPGpp) guideline, which can cause aortic thickening, stiffening, and dysfunction. This study sought to find the BPGpp severity and duration that avoid persistent dysfunction in a preclinical model and test if predictors translate to hypertension status in patients with CoA. METHODS: Rabbits (n=75; 5–12/group) were exposed to mild, intermediate, or severe CoA (≤12, 13–19, ≥20 mm Hg BPGpp) for ≈1, 3, or 22 weeks using dissolvable and permanent sutures with thickening, stiffening, contraction, and endothelial function evaluated via multivariate regression. Relevance to patients with CoA (n=239; age, 0.01–46 years; median 3.7 months) was tested by retrospective review of predictors (preoperative BPGpp, surgical age, etc.) versus follow-up hypertension status. RESULTS: CoA duration and severity were predictive of aortic remodeling and active dysfunction in rabbits, and hypertension in patients with CoA. Interaction between patient age and BPGpp at surgery contributed significantly to hypertension, similar to rabbits, suggesting preclinical findings translate to patients. Machine learning decision tree analysis uncovered that preoperative BPGpp and surgical age predict risk of hypertension along with residual postoperative BPGpp. CONCLUSIONS: These findings suggest the current BPGpp threshold determined decades ago is likely too high to prevent adverse coarctation-induced aortic remodeling. The results and decision tree analysis provide a foundation for revising CoA treatment guidelines considering the interaction between CoA severity and duration to limit the risk of hypertension.