Division 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.).
Department of Biomedical Engineering, Marquette University and the Medical College of Wisconsin, Milwaukee, (A.G., J.F.L.D.).
Hypertension. 2024 May;81(5):1115-1124. doi: 10.1161/HYPERTENSIONAHA.123.22142. Epub 2024 Mar 19.
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.
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.
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.
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.
主动脉缩窄（CoA）治疗后常导致高血压。目前的 20mmHg 峰-峰血压（BP）梯度（BPGpp）指南缺乏证据，该指南可能导致主动脉增厚、僵硬和功能障碍。本研究旨在寻找避免临床前模型中持续功能障碍的 BPGpp 严重程度和持续时间，并检验 CoA 患者中预测因子是否转化为高血压状态。
通过可溶解和永久性缝线，使兔子（n=75；5-12/组）暴露于轻度、中度或重度 CoA（≤12、13-19、≥20mmHg BPGpp）中，持续 ≈1、3 或 22 周，采用多元回归评估增厚、僵硬、收缩和内皮功能。通过回顾性分析预测因子（术前 BPGpp、手术年龄等）与随访高血压状态，检验其与 CoA 患者（n=239；年龄 0.01-46 岁；中位数 3.7 个月）的相关性。
CoA 持续时间和严重程度可预测兔子主动脉重塑和主动功能障碍，以及 CoA 患者的高血压。患者年龄与手术时 BPGpp 的相互作用对高血压有显著影响，与兔子相似，表明临床前发现可转化为患者。机器学习决策树分析显示，术前 BPGpp 和手术年龄与术后残余 BPGpp 一起预测高血压风险。
这些发现表明，几十年前确定的当前 BPGpp 阈值可能过高，无法预防不良 CoA 引起的主动脉重塑。这些结果和决策树分析为修订 CoA 治疗指南提供了基础，考虑到 CoA 严重程度和持续时间的相互作用，以限制高血压的风险。
