Department of Pediatrics, Stollery Children's Hospital, Edmonton, Canada (J.C.).
Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada (S. Min, S. Mital).
Circulation. 2023 Feb 28;147(9):718-727. doi: 10.1161/CIRCULATIONAHA.122.062699. Epub 2022 Nov 6.
Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, abnormal results on exercise stress testing are predictive of heart failure outcomes. Our goal was to determine whether an abnormal exercise response is associated with adverse outcomes in pediatric patients with HCM.
In an international cohort study including 20 centers, phenotype-positive patients with primary HCM who were <18 years of age at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response and new or worsened ST- or T-wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of abnormal exercise test results with transplant and SCD event-free survival.
Of 724 eligible patients, 630 underwent at least 1 exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8 years (interquartile range, 4.7 years); 78% were male and 39% were receiving beta-blockers. A total of 175 (28%) had abnormal test results. Patients with abnormal test results had more severe septal hypertrophy, higher left atrial diameter scores, higher resting left ventricular outflow tract gradient, and higher frequency of myectomy compared with participants with normal test results (<0.05). Compared with normal test results, abnormal test results were independently associated with lower 5-year transplant-free survival (97% versus 88%, respectively; =0.005). Patients with exercise-induced ischemia were most likely to experience all-cause death or transplant (hazard ratio, 4.86 [95% CI, 1.69-13.99]), followed by those with an abnormal blood pressure response (hazard ratio, 3.19 [95% CI, 1.32-7.71]). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (hazard ratio, 3.32 [95% CI, 1.27-8.70]). Exercise-induced ectopy was not associated with survival.
Exercise abnormalities are common in childhood HCM. An abnormal exercise test result was independently associated with lower transplant-free survival, especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.
肥厚型心肌病（HCM）可与异常的运动反应有关。在患有 HCM 的成年人中，运动应激试验异常结果可预测心力衰竭结局。我们的目标是确定异常运动反应是否与儿科 HCM 患者的不良结局相关。
在一项包括 20 个中心的国际队列研究中，纳入了在诊断时年龄<18 岁的原发性 HCM 且表型阳性的患者。异常运动反应定义为血压反应减弱，新发或加重的 ST 段或 T 波段改变或复杂室性心律失常。心脏性猝死（SCD）事件定义为 SCD 和心搏骤停中止的复合事件。使用 Kaplan-Meier 生存、竞争结局和 Cox 回归分析，我们分析了异常运动试验结果与移植和 SCD 无事件生存的关系。
在 724 名符合条件的患者中，有 630 名患者至少进行了 1 次运动试验。进行或未进行运动试验的患者在临床特征方面无明显差异。运动试验时的中位年龄为 13.8 岁（四分位距，4.7 岁）；78%为男性，39%正在服用β受体阻滞剂。共有 175 名（28%）患者的试验结果异常。与正常试验结果相比，异常试验结果的患者间隔肥厚更严重，左心房直径分数更高，静息左心室流出道梯度更高，接受心肌切除术的频率也更高（<0.05）。与正常试验结果相比，异常试验结果与较低的 5 年移植无生存相关（分别为 97%和 88%；=0.005）。运动诱导缺血的患者最有可能经历全因死亡或移植（风险比，4.86[95%CI，1.69-13.99]），其次是血压反应异常的患者（风险比，3.19[95%CI，1.32-7.71]）。运动诱导的缺血也与较低的 SCD 无事件生存独立相关（风险比，3.32[95%CI，1.27-8.70]）。运动诱导的室性心律失常与生存无关。
运动异常在儿童 HCM 中很常见。异常运动试验结果与较低的移植无生存相关，特别是在运动时出现缺血或血压反应异常的患者中。运动诱导的缺血也与 SCD 事件独立相关。这些发现支持将常规运动测试作为儿童 HCM 持续风险评估的一部分。
