重新审视乌地那非对Fontan循环患者运动能力的影响：FUEL试验的事后分析结果
Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial.
作者信息
Goldberg David J, Zak Victor, Hu Chenwei, Lubert Adam M, Rathod Rahul H, Penny Daniel J, Whitehill Robert, Schumacher Kurt R, Ginde Salil, Ploutz Michelle, Kim Gi Beom, Nowlen Todd T, DiMaria Michael V, Frischhertz Benjamin P, Wagner Jonathan B, McHugh Kimberly E, McCrindle Brian W, Cartoski Mark J, Detterich Jon, Yetman Anji T, John Anitha S, Richmond Marc E, Files Matthew, Payne R Mark, Mackie Andrew S, Davis Christopher K, Orr William B, Garg Ruchira, Hill Kevin D, Yauck Jennifer S, McBride Michael G, Yeager James, Pearson Gail D, Paridon Stephen M, Goldstein Bryan H
机构信息
Division of Cardiology The Children's Hospital of Philadelphia, Perelman School of Medicine Philadelphia PA USA.
Carelon Research Newton MA USA.
出版信息
J Am Heart Assoc. 2025 Aug 19;14(16):e041348. doi: 10.1161/JAHA.125.041348. Epub 2025 Aug 12.
BACKGROUND
In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo) at peak exercise. This disparate response may be explained by the physiologic challenge of improving peak Vo in participants with near-normal baseline exercise performance.
METHODS
Participants were divided into subgroups by baseline predicted peak Vo (<80% versus ≥80%). Treatment effect was evaluated in those with a baseline peak Vo <80% predicted and linear regression was performed to examine the interaction between subgroup and response to therapy for the primary and secondary outcomes.
RESULTS
Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak Vo <80% predicted. In this subgroup, the primary outcome of peak Vo improved significantly after 6 months of udenafil treatment, when compared with placebo (0.23±4.17 mL/kg per min versus -0.90±3.74 mL/kg per min; =0.021). Secondary outcome measures, including Vo at ventilatory anaerobic threshold (=0.023), work at ventilatory anaerobic threshold (=0.032), and the myocardial performance index (=0.007) were all significantly improved as well. A significant interaction was found between exercise subgroups and response to udenafil for peak Vo (=0.036) but not for other outcomes.
CONCLUSIONS
In this post hoc subgroup analysis, after exclusion of patients with Fontan circulation with near-normal baseline peak Vo, a positive treatment effect of udenafil was identified for the primary outcome of peak Vo. The interaction between baseline peak Vo and treatment may have influenced the outcome of the FUEL trial.
REGISTRATION
URL: https://clinicaltrials.gov; Unique identifier: NCT0274115.
背景
在FUEL（Fontan环丙沙星运动纵向）试验中，已确定通气无氧阈值时的结果有积极的治疗效果，但对于主要结果，即运动峰值时的耗氧量（Vo）则没有。这种不同的反应可能是由于在基线运动表现接近正常的参与者中提高峰值Vo的生理挑战所致。
方法
参与者按基线预测峰值Vo（<80% 与≥80%）分为亚组。对基线峰值Vo<80%预测值的患者评估治疗效果，并进行线性回归以检查亚组与主要和次要结果的治疗反应之间的相互作用。
结果
在379名有配对运动数据的参与者中，302名（80%）基线峰值Vo<80%预测值。在该亚组中，与安慰剂相比，服用环丙沙星6个月后，峰值Vo的主要结果有显著改善（分别为0.23±4.17毫升/千克每分钟和 -0.90±3.74毫升/千克每分钟；P=0.021）。次要结果指标，包括通气无氧阈值时的Vo（P=0.023）、通气无氧阈值时的功（P=0.032）和心肌性能指数（P=0.007）也均有显著改善。运动亚组与环丙沙星对峰值Vo的反应之间存在显著相互作用（P=0.036），但对其他结果则不存在。
结论
在这项事后亚组分析中，排除基线峰值Vo接近正常的Fontan循环患者后，确定环丙沙星对峰值Vo的主要结果有积极治疗效果。基线峰值Vo与治疗之间的相互作用可能影响了FUEL试验的结果。
注册
网址：https://clinicaltrials.gov；唯一标识符：NCT0274115 。
需注意，原文中“Vo”可能表述有误，应为“VO₂”，即耗氧量，翻译时按原文进行了翻译。同时，原文中“=0.021”等表述可能是记录数据时的简略写法，完整表述可能是“P = 0.021”等，这里也按原文进行了翻译。
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