Liu Hong, Qian Si-Chong, Shao Yong-Feng, Li Hai-Yang
Department of Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.
Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People's Republic of China.
J Inflamm Res. 2022 Jun 27;15:3709-3718. doi: 10.2147/JIR.S369703. eCollection 2022.
Acute type A aortic dissection (ATAAD) is a heterogeneous systemic inflammatory response syndrome. Identification of distinct inflammatory phenotypes may allow more precise therapy and improved care. We aim to investigate whether distinct inflammatory subphenotypes exist in ATAAD patients and respond differently to pharmacotherapies.
Retrospective analysis of data sets was conducted from the Additive Anti-inflammatory Actions for Aortopathy & Arteriopathy (5A) III study. Inflammatory subphenotypes were derived among 2008 ATAAD patients who received surgical repair at 11 Chinese hospitals (2016-2020) using latent class analysis applied to 14 laboratory signatures within 6 hours of hospital admission. Outcomes included operative mortality (Society of Thoracic Surgeons definition), derived subphenotype frequency, and the potential consequences of phenotype frequency distributions on the treatment effects.
The median (interquartile range) age of patients was 54 (45-62) years, and 1423 (70.9%) were male. A two-class (two subphenotype) model was an improvement over a one-class model (<·001), with 1451 (72.3%) patients in the hypoinflammatory subphenotype group and 557 (27.7%) in the hyperinflammatory subphenotype group. Patients with the hyperinflammatory subphenotype had higher operative mortality (71 [12.7%] vs 127 [8.8%]; =0·007) than did those with the hypoinflammatory subphenotype. Furthermore, the interaction between ulinastatin treatment and subphenotype is not significant for operative mortality (=0.15) but for ventilator time (=0·04).
Two subphenotypes of ATAAD were identified in the 5A cohort that correlated with clinical outcomes, with significant interaction effect between anti-inflammatory treatment and subphenotypes for ventilator time, suggesting these phenotypes may help in understanding heterogeneity of treatment effects.
Clinical Trials. Gov: number NCT04918108.
急性A型主动脉夹层（ATAAD）是一种异质性全身炎症反应综合征。识别不同的炎症表型可能有助于更精确的治疗并改善护理。我们旨在研究ATAAD患者中是否存在不同的炎症亚表型，以及它们对药物治疗的反应是否不同。
对主动脉病和动脉病的附加抗炎作用（5A）III研究的数据集进行回顾性分析。在11家中国医院（2016 - 2020年）接受手术修复的2008例ATAAD患者中，使用潜在类别分析对入院6小时内的14项实验室指标进行分析，得出炎症亚表型。结局指标包括手术死亡率（胸外科医师协会定义）、得出的亚表型频率，以及表型频率分布对治疗效果的潜在影响。
患者的中位（四分位间距）年龄为54（45 - 62）岁，1423例（70.9%）为男性。与单类别模型相比，双类别（两个亚表型）模型有所改进（<·001），低炎症亚表型组有1451例（72.3%）患者，高炎症亚表型组有557例（27.7%）患者。高炎症亚表型患者的手术死亡率高于低炎症亚表型患者（71例[12.7%]对127例[8.8%]；=0·007）。此外，乌司他丁治疗与亚表型之间的相互作用对手术死亡率不显著（=0.15），但对呼吸机使用时间显著（=0·04）。
在5A队列中识别出两种ATAAD亚表型，它们与临床结局相关，抗炎治疗与亚表型之间对呼吸机使用时间有显著的相互作用，提示这些表型可能有助于理解治疗效果的异质性。
临床试验。Gov：编号NCT04918108。
