Coarctation duration and severity predict the likelihood of hypertension precursors in a preclinical model and hypertensive status among patients

Coarctation of the aorta (CoA) often leads to hypertension (HTN) post-treatment. There is limited evidence for the current ≥20 mmHg peak-to-peak blood pressure gradient (BPGpp) guideline, which can cause aortic thickening, stiffening and dysfunction. This study sought to find the BPGpp severity and duration that avoids persistent dysfunction in a preclinical model, and test if predictors identified translate to HTN status in CoA patients. Rabbits (N=75; 5–11/group; 10 weeks-old) were exposed to mild, intermediate or severe CoA (≤12, 13–19 & ≥20 mmHg BPGpp) for ~1, 3 or 22 weeks using dissolvable and permanent sutures with thickening, stiffening, contraction and endothelial function evaluated via multivariate regression analysis. The relevance of findings to CoA patients (N=239; age=0.01–46 years; mean 3.44 years) was similarly tested by retrospective review of predictors (pre-operative BPGpp, age at surgery, etc) vs follow-up HTN status. CoA duration and severity were predictive of remodeling and dysfunction in rabbits and HTN likelihood in CoA patients. Interaction between patient age and BPGpp at surgery were significant contributors to HTN, suggesting preclinical findings translate to human. Machine-learning decision tree analysis uncovered duration and severity values for precursors of HTN in the preclinical model, and HTN at follow-up in CoA patients. These findings suggest the current BPGpp threshold is likely too high to limit activation of processes leading to persistent aortic changes associated with HTN. The resulting decision tree provides a foundation for revising CoA treatment guidelines by considering the interaction between CoA severity and duration to limit the chance of HTN.