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Coarctation Duration and Severity Predict Risk of Hypertension Precursors in a Preclinical Model and Hypertensive
Arash Ghorbannia1,2,3, Hilda Jurkiewicz1, Lith Nasif4
1Division of Cardiology, Department of Pediatrics, Herma Heart Institute, Children's Wisconsin and the Medical College of Wisconsin, Milwaukee, (A.G., H.J., J.F.L.D.).
Insights
The current guideline for coarctation of the aorta (CoA) treatment may be too high, leading to persistent hypertension. Lowering the peak-to-peak blood pressure gradient (BPGpp) threshold could prevent aortic remodeling and dysfunction.
Area of Science:
- Cardiovascular Research
- Medical Engineering
- Hypertension Studies
Background:
- Coarctation of the aorta (CoA) frequently results in post-treatment hypertension.
- Current guidelines for peak-to-peak blood pressure gradient (BPGpp) >20 mm Hg lack evidence and may cause aortic complications.
- Persistent aortic dysfunction and hypertension are significant concerns after CoA treatment.
Purpose of the Study:
- To determine the severity and duration of BPGpp that prevent persistent aortic dysfunction in a preclinical model.
- To assess if predictors of aortic dysfunction in the preclinical model translate to hypertension in human patients with CoA.
- To evaluate the current BPGpp guideline's adequacy in preventing adverse aortic remodeling.
Main Methods:
- A preclinical rabbit model was used to induce mild, intermediate, or severe CoA for varying durations (≈1, 3, or 22 weeks).
- Aortic thickening, stiffening, contraction, and endothelial function were assessed using multivariate regression.
- Retrospective analysis of 239 patients with CoA evaluated predictors (preoperative BPGpp, surgical age) against hypertension status.
Main Results:
- CoA severity and duration predicted aortic remodeling and dysfunction in rabbits, and hypertension in patients.
- The interaction between patient age and surgical BPGpp significantly contributed to hypertension, mirroring preclinical findings.
- Machine learning identified preoperative BPGpp, surgical age, and residual postoperative BPGpp as key predictors of hypertension risk.
Conclusions:
- The existing BPGpp threshold for CoA treatment is likely too high, contributing to adverse aortic remodeling.
- Findings support revising CoA treatment guidelines to incorporate CoA severity and duration interactions.
- Reducing the BPGpp threshold may mitigate the risk of developing hypertension post-treatment.
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.
