Frank Benjamin S, Niemiec Sierra, Khailova Ludmila, Mancuso Christopher A, Mitchell Max B, Morgan Gareth J, Twite Mark, DiMaria Michael V, Sucharov Carmen C, Davidson Jesse A
Section of Cardiology, Department of Pediatrics, University of Colorado, Aurora, Colorado, USA.
Department of Biostatistics and Informatics, University of Colorado, Aurora, Colorado, USA.
JACC Adv. 2025 Apr;4(4):101672. doi: 10.1016/j.jacadv.2025.101672. Epub 2025 Mar 20.
Endothelin-1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle cell proliferation. We previously demonstrated that failure to suppress ET1 is associated with morbidity in infants with single ventricle heart disease (SVHD) undergoing stage 2 palliation.
The aim of this study is to evaluate whether persistent failure to suppress ET1 is associated with impaired recovery among children with SVHD undergoing the stage 3 (Fontan) operation.
A prospective cohort study that includes 84 children with SVHD undergoing stage 3 palliation and 50 controls. Samples for ET1 analysis were collected at preoperation (systemic and pulmonary vein), 2, 24, and 48 hours postoperation for SVHD cases and a single timepoint for controls. Primary outcomes were Fontan pressure and systemic oxygen saturation at 24 hours postoperation.
SVHD cases showed higher ET1 in the systemic vein than pulmonary vein (1.0 vs 0.7 pg/mL, P < 0.001) and lower systemic vein levels than controls (1.0 vs 1.4 pg/mL, P = 0.001). Among cases, ET1 concentration peaked at 2 hours postoperation, decreased by 24 hours, and was stable but not back to baseline by 48 hours. Adjusting for clinical covariates, higher preoperative ET1 was associated with higher 24-hour Fontan pressure. Higher 24-hour postoperative ET1 was associated with lower systemic oxygen saturation at 24 hours postoperation, higher 24-hour Fontan pressure, more pleural drainage, and longer length of stay.
SVHD children with higher peri-operative ET1 experience more post-stage 3 morbidity. Failure to suppress ET1 may be a modifiable risk factor for intolerance of SVHD palliation.
内皮素 -1（ET1）是一种强效的血管收缩剂，也是肺动脉平滑肌细胞增殖的刺激物。我们之前证明，未能抑制ET1与接受二期姑息治疗的单心室心脏病（SVHD）婴儿的发病率相关。
本研究的目的是评估持续未能抑制ET1是否与接受三期（Fontan）手术的SVHD儿童恢复受损有关。
一项前瞻性队列研究，纳入84例接受三期姑息治疗的SVHD儿童和50例对照。SVHD病例在术前（体循环和肺静脉）、术后2小时、24小时和48小时采集用于ET1分析的样本，对照仅采集一个时间点的样本。主要结局是术后24小时的Fontan压力和体循环血氧饱和度。
SVHD病例体循环静脉中的ET1高于肺静脉（1.0对0.7 pg/mL，P < 0.001），且体循环静脉水平低于对照（1.0对1.4 pg/mL，P = 0.001）。在病例中，ET1浓度在术后2小时达到峰值，24小时下降，48小时时稳定但未恢复到基线水平。调整临床协变量后，术前ET1较高与术后24小时Fontan压力较高相关。术后24小时ET1较高与术后24小时体循环血氧饱和度较低、术后24小时Fontan压力较高、胸腔引流量较多及住院时间较长相关。
围手术期ET1较高的SVHD儿童三期术后发病率更高。未能抑制ET1可能是SVHD姑息治疗不耐受的一个可改变的危险因素。
